Structural and functional characteristics of rat hearts with and without myocardial infarct. Initial experience with doppler echocardiography

OBJECTIVE: To assess by Doppler echocardiography the structural and functional alterations of rat heart with surgical induced extensive myocardial infarction. METHODS: Five weeks after surgical ligature of the left coronary artery, 38 Wistar-EPM rats of both sexes, 10 of them with extensive infarction, undergone anatomical and functional evaluation by Doppler echocardiography and then euthanized for anatomopathological analysis. RESULTS: Echocardiography was 100% sensible and specific to anatomopathological confirmed extensive miocardial infarction. Extensive infarction lead to dilatation of left ventricle (diastolic diameter: 0.89cm vs.0.64cm; systolic: 0.72cm vs. 0.33cm) and left atrium (0.55cm vs. 0.33cm); thinning of left ventricular anterior wall (systolic: 0.14cm vs. 0.23cm, diastolic: 0.11cm vs. 0.14cm); increased mitral E/ A wave relation (6.45 vs. 1.95). Signals of increased end diastolic ventricle pressure, B point in mitral valve tracing in 62.5% and signs of pulmonary hypertension straightening of pulmonary valve (90%) and notching of pulmonary systolic flow (60%) were observed in animals with extensive infarction. CONCLUSION: Doppler echocardiography has a high sensitivity and specificity for detection of chronic extensive infarction. Extensive infarction caused dilatation of left cardiac chambers and showed in Doppler signals of increased end diastolic left ventricular pressure and pulmonary artery pressure.

End-systolic pressure-diameter relation of the left ventricle during transient and sustained elevations of blood pressure

OBJECTIVE: To assess the effect of transient and sustained variations in cardiac load on the values of the end-systolic pressure-diameter relation (ESPDR) of the left ventricle. METHODS: We studied 13 dogs under general anesthesia and autonomic blockade. Variations of cardiac loads were done by elevation of blood pressure by mechanical constriction of the aorta. Two protocols were used in each animal: gradual peaking and decreasing pressure variation, the "transient arterial hypertension protocol" (TAH), and a quick and 10 min sustained elevation, the "sustained arterial hypertension protocol"(SAH). Then, we compared the ESDR in these two situations. RESULTS: Acute elevation of arterial pressure, being it "transitory" or "sustained", did not alter the heart frequency and increased similarly the preload and after load. However, they acted differently in end systolic pressure-diameter relation. It was greater in the SAH than TAH protocol, 21.0±7.3mmHg/mm vs. 9.2±1.2mmHg/mm (p<0.05). CONCLUSION: The left ventricular ESPDR values determined during sustained pressure elevations were higher than those found during transient pressure elevations. The time-dependent activation of myocardial contractility associated with the Frank-Starling mechanism is the major factor in inotropic stimulation during sustained elevations of blood pressure, determining an increase in the ESPDR values.

Effects of an exercise program on blood pressure in patients with treated hypertension and chronic Chagas' heart disease

INTRODUCTION: Previous studies describe an imbalance of the autonomic nervous system in Chagas' disease causing increased sympathetic activity, which could influence the genesis of hypertension. However, patients undergoing regular physical exercise could counteract this condition, considering that exercise causes physiological responses through autonomic and hemodynamic changes that positively affect the cardiovascular system. This study aimed to evaluate the effects of an exercise program on blood pressure in hypertensive patients with chronic Chagas' heart disease. METHODS: We recruited 17 patients to a 24-week regular exercise program and used ambulatory blood pressure monitoring before and after training. We determined the differences in the systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) from the beginning to the end of the study. RESULTS: The blood pressures were evaluated in general and during periods of wakefulness and sleep, respectively: SBP (p = 0.34; 0.23; 0.85), DBP (p = 0.46; 0.44; 0.94) and MBP (p = 0.41; 0.30; 0.97). CONCLUSIONS: There was no statistically significant change in blood pressure after the 24-week exercise program; however, we concluded that physical training is safe for patients with chronic Chagas' disease, with no incidence of increase in blood pressure.

Ambulatory blood pressure monitoring of patients with heart failure: a new prognosis marker

OBJECTIVE: To evaluate the relationship between 24-hour ambulatory arterial blood pressure monitoring and the prognosis of patients with advanced congestive heart failure. METHODS: We studied 38 patients with NYHA functional class IV congestive heart failure, and analyzed left ventricular ejection fraction, diastolic diameter, and ambulatory blood pressure monitoring data. RESULTS: Twelve deaths occurred. Left ventricular ejection fraction (35.2±7.3%) and diastolic diameter (72.2±7.8mm) were not correlated with the survival. The mean 24-hour (SBP24), waking (SBPw), and sleeping (SBPs) systolic pressures of the living patients were higher than those of the deceased patients and were significant for predicting survival. Patients with mean SBP24, SBPv, and SBPs > or = 105mmHg had longer survival (p=0.002, p=0.01 and p=0.0007, respectively). Patients with diastolic blood pressure sleep decrements (dip) and patients with mean blood pressure dip <=6mmHg had longer survival (p=0.04 and p=0.01, respectively). In the multivariate analysis, SBPs was the only variable with an odds ratio of 7.61 (CI: 1.56; 3704) (p=0.01). Patients with mean SBP<105mmHg were 7.6 times more likely to die than those with SBP > or = 105 mmHg CONCLUSION: Ambulatory blood pressure monitoring appears to be a useful method for evaluating patients with congestive heart failure.

Benefits of exercise training in the treatment of heart failure: study with a control group

OBJECTIVE: Exercise training programs have been proposed as adjuncts to treatment of heart failure. The effects of a 3-month-exercise-training-program with 3 exercise sessions per week were assessed in patients with stable systolic chronic heart failure. METHODS: We studied 24 patients with final left ventricle diastolic diameter of 70±10mm and left ventricular ejection fraction of 37±4%. Mean age was 52±16 years. Twelve patients were assigned to an exercise training group (G1), and 12 patients were assigned to a control group (G2). Patients underwent treadmill testing, before and after exercise training, to assess distance walked, heart rate, systolic blood pressure, and double product. RESULTS: In G2 group, before and after 3 months, we observed, respectively distance walked, 623±553 and 561± 460m (ns); peak heart rate, 142±23 and 146± 33b/min (ns); systolic blood pressure, 154±36 and 164±26 mmHg (ns); and double product, 22211± 6454 and 24293±7373 (ns). In G1 group, before and after exercise, we observed: distance walked, 615±394 and 970± 537m (p<0.003) peak heart rate, 143±24 and 143±29b/min (ns); systolic blood pressure, 136±33 and 133±24 mmHg (ns); and double product, 19907± 7323 and 19115±5776, respectively. Comparing the groups, a significant difference existed regarding the variation in the double product, and in distance walked. CONCLUSION: Exercise training programs in patients with heart failure can bring about an improvement in physical capacity.

Subendocardial fibrosis in remote myocardium results from reduction of coronary driving pressure during acute infarction in rats

OBJECTIVE: To investigate the role of hemodynamic changes occurring during acute MI in subsequent fibrosis deposition within non-MI. METHODS: By using the rat model of MI, 3 groups of 7 rats each [sham, SMI (MI <30%), and LMI (MI >30%)] were compared. Systemic and left ventricular (LV) hemodynamics were recorded 10 minutes before and after coronary artery ligature. Collagen volume fraction (CVF) was calculated in picrosirius red-stained heart tissue sections 4 weeks later. RESULTS: Before surgery, all hemodynamic variables were comparable among groups. After surgery, LV end-diastolic pressure increased and coronary driving pressure decreased significantly in the LMI compared with the sham group. LV dP/dt max and dP/dt min of both the SMI and LMI groups were statistically different from those of the sham group. CVF within non-MI interventricular septum and right ventricle did not differ between each MI group and the sham group. Otherwise, subendocardial (SE) CVF was statistically greater in the LMI group. SE CVF correlated negatively with post-MI systemic blood pressure and coronary driving pressure, and positively with post-MI LV dP/dt min. Stepwise regression analysis identified post-MI coronary driving pressure as an independent predictor of SE CVF. CONCLUSION: LV remodeling in rats with MI is characterized by predominant SE collagen deposition in non-MI and results from a reduction in myocardial perfusion pressure occurring early on in the setting of MI.

Heart Rate and Systolic Blood Pressure Variability on Recently Diagnosed Diabetics

Background:Diabetes affects approximately 250 million people in the world. Cardiovascular autonomic neuropathy is a common complication of diabetes that leads to severe postural hypotension, exercise intolerance, and increased incidence of silent myocardial infarction.Objective:To determine the variability of heart rate (HR) and systolic blood pressure (SBP) in recently diagnosed diabetic patients.Methods:The study included 30 patients with a diagnosis of type 2 diabetes of less than 2 years and 30 healthy controls. We used a Finapres® device to measure during five minutes beat-to-beat HR and blood pressure in three experimental conditions: supine position, standing position, and rhythmic breathing at 0.1 Hz. The results were analyzed in the time and frequency domains.Results:In the HR analysis, statistically significant differences were found in the time domain, specifically on short-term values such as standard deviation of NN intervals (SDNN), root mean square of successive differences (RMSSD), and number of pairs of successive NNs that differ by more than 50 ms (pNN50). In the BP analysis, there were no significant differences, but there was a sympathetic dominance in all three conditions. The baroreflex sensitivity (BRS) decreased in patients with early diabetes compared with healthy subjects during the standing maneuver.Conclusions:There is a decrease in HR variability in patients with early type 2 diabetes. No changes were observed in the BP analysis in the supine position, but there were changes in BRS with the standing maneuver, probably due to sympathetic hyperactivity.

Lowering Pulmonary Wedge Pressure after Heart Transplant: Pulmonary Compliance and Resistance Effect

AbstractBackground:Right ventricular (RV) afterload is an important risk factor for post-heart transplantation (HTx) mortality, and it results from the interaction between pulmonary vascular resistance (PVR) and pulmonary compliance (CPA). Their product, the RC time, is believed to be constant. An exception is observed in pulmonary hypertension because of elevated left ventricular (LV) filling pressures.Objective:Using HTx as a model for chronic lowering of LV filling pressures, our aim was to assess the variations in RV afterload components after transplantation.Methods:We retrospectively studied 159 patients with right heart catheterization before and after HTx. The effect of Htx on hemodynamic variables was assessed.Results:Most of the patients were male (76%), and the mean age was 53 ± 12 years. HTx had a significant effect on the hemodynamics, with normalization of the LV and RV filling pressures and a significant increase in cardiac output and heart rate (HR). The PVR decreased by 56% and CPA increased by 86%. The RC time did not change significantly, instead of increasing secondary to pulmonary wedge pressure (PWP) normalization after HTx as expected. The expected increase in RC time with PWP lowering was offset by the increase in HR (because of autonomic denervation of the heart). This effect was independent from the decrease of PWP.Conclusion:The RC time remained unchanged after HTx, notwithstanding the fact that pulmonary capillary wedge pressure significantly decreased. An increased HR may have an important effect on RC time and RV afterload. Studying these interactions may be of value to the assessment of HTx candidates and explaining early RV failure after HTx.

Palliative Senning in the Treatment of Congenital Heart Disease with Severe Pulmonary Hypertension

Background:Transposition of the great arteries (TGA) is the most common cyanotic cardiopathy, with an incidence ranging between 0.2 and 0.4 per 1000 live births. Many patients not treated in the first few months of life may progress with severe pulmonary vascular disease. Treatment of these patients may include palliative surgery to redirect the flow at the atrial level.Objective:Report our institutional experience with the palliative Senning procedure in children diagnosed with TGA and double outlet right ventricle with severe pulmonary vascular disease, and to evaluate the early and late clinical progression of the palliative Senning procedure.Methods:Retrospective study based on the evaluation of medical records in the period of 1991 to 2014. Only patients without an indication for definitive surgical treatment of the cardiopathy due to elevated pulmonary pressure were included.Results:After one year of follow-up there was a mean increase in arterial oxygen saturation from 62.1% to 92.5% and a mean decrease in hematocrit from 49.4% to 36.3%. Lung histological analysis was feasible in 16 patients. In 8 patients, pulmonary biopsy grades 3 and 4 were evidenced.Conclusion:The palliative Senning procedure improved arterial oxygen saturation, reduced polycythemia, and provided a better quality of life for patients with TGA with ventricular septal defect, severe pulmonary hypertension, and poor prognosis.

Increased angiotensin-converting enzyme activity in the left ventricle after infarction

An increase in angiotensin-converting enzyme (ACE) activity has been observed in the heart after myocardial infarction (MI). Since most studies have been conducted in chronically infarcted individuals exhibiting variable degrees of heart failure, the present study was designed to determine ACE activity in an earlier phase of MI, before heart failure development. MI was produced in 3-month old male Wistar rats by ligation of the anterior branches of the left coronary artery, control rats underwent sham surgery and the animals were studied 7 or 15 days later. Hemodynamic data obtained for the anesthetized animals showed normal values of arterial blood pressure and of end-diastolic pressure in the right and left ventricular cavities of MI rats. Right and left ventricular (RV, LV) muscle and scar tissue homogenates were prepared to determine ACE activity in vitro by measuring the velocity of His-Leu release from the synthetic substrate Hyp-His-Leu. ACE activity was corrected to the tissue wet weight and is reported as nmol His-Leu g-1 min-1. No significant change in ACE activity in the RV homogenates was demonstrable. A small nonsignificant increase of ACE activity (11 &plusmn; 9%; P0.05) was observed 7 days after MI in the surviving left ventricular muscle. Two weeks after surgery, however, ACE activity was 46 &plusmn; 11% (P<0.05) higher in infarcted rats compared to sham-operated rats. The highest ACE activity was demonstrable in the scar tissue homogenate. In rats studied two weeks after surgery, ACE activity in the LV muscle increased from 105 &plusmn; 7 nmol His-Leu g-1 min-1 in control hearts to 153 &plusmn; 11 nmol His-Leu g-1 min-1 (P<0.05) in the remaining LV muscle of MI rats and to 1051 &plusmn; 208 nmol His-Leu g-1 min-1 (P<0.001) in the fibrous scar. These data indicate that ACE activity increased in the heart after infarction before heart failure was demonstrable by hemodynamic measurements. Since the blood vessels of the scar drain to the remaining LV myocardium, the high ACE activity present in the fibrous scar may increase the angiotensin II concentration and decrease bradykinin in the cardiac tissues surrounding the infarcted area. The increased angiotensin II in the fibrous scar may contribute to the reactive fibrosis and hypertrophy in the left ventricular muscle surviving infarction

Time course of changes in heart rate and blood pressure variability in streptozotocin-induced diabetic rats treated with insulin

Autonomic neuropathy is a frequent complication of diabetes associated with higher morbidity and mortality in symptomatic patients, possibly because it affects autonomic regulation of the sinus node, reducing heart rate (HR) variability which predisposes to fatal arrhythmias. We evaluated the time course of arterial pressure and HR and indirectly of autonomic function (by evaluation of mean arterial pressure (MAP) variability) in rats (164.5 ± 1.7 g) 7, 14, 30 and 120 days after streptozotocin (STZ) injection, treated with insulin, using measurements of arterial pressure, HR and MAP variability. HR variability was evaluated by the standard deviation of RR intervals (SDNN) and root mean square of successive difference of RR intervals (RMSSD). MAP variability was evaluated by the standard deviation of the mean of MAP and by 4 indices (P1, P2, P3 and MN) derived from the three-dimensional return map constructed by plotting MAPn x [(MAPn+1) - (MAPn)] x density. The indices represent the maximum concentration of points (P1), the longitudinal axis (P2), and the transversal axis (P3) and MN represents P1 x P2 x P3 x 10-3. STZ induced increased urinary glucose in diabetic (D) rats compared to controls (C). Seven days after STZ, diabetes reduced resting HR from 380.6 ± 12.9 to 319.2 ± 19.8 bpm, increased HR variability, as demonstrated by increased SDNN, from 11.77 ± 1.67 to 19.87 ± 2.60 ms, did not change MAP, and reduced P1 from 61.0 ± 5.3 to 51.5 ± 1.8 arbitrary units (AU), P2 from 41.3 ± 0.3 to 29.0 ± 1.8 AU, and MN from 171.1 ± 30.2 to 77.2 ± 9.6 AU of MAP. These indices, as well as HR and MAP, were similar for D and C animals 14, 30 and 120 days after STZ. Seven-day rats showed a negative correlation of urinary glucose with resting HR (r = -0.76, P = 0.03) as well as with the MN index (r = -0.83, P = 0.01). We conclude that rats with short-term diabetes mellitus induced by STZ presented modified autonomic control of HR and MAP which was reversible. The metabolic control may influence these results, suggesting that insulin treatment and a better metabolic control in this model may modify arterial pressure, HR and MAP variability

Post-exercise changes in blood pressure, heart rate and rate pressure product at different exercise intensities in normotensive humans

To evaluate the effect of exercise intensity on post-exercise cardiovascular responses, 12 young normotensive subjects performed in a randomized order three cycle ergometer exercise bouts of 45 min at 30, 50 and 80% of VO2peak, and 12 subjects rested for 45 min in a non-exercise control trial. Blood pressure (BP) and heart rate (HR) were measured for 20 min prior to exercise (baseline) and at intervals of 5 to 30 (R5-30), 35 to 60 (R35-60) and 65 to 90 (R65-90) min after exercise. Systolic, mean, and diastolic BP after exercise were significantly lower than baseline, and there was no difference between the three exercise intensities. After exercise at 30% of VO2peak, HR was significantly decreased at R35-60 and R65-90. In contrast, after exercise at 50 and 80% of VO2peak, HR was significantly increased at R5-30 and R35-60, respectively. Exercise at 30% of VO2peak significantly decreased rate pressure (RP) product (RP = HR x systolic BP) during the entire recovery period (baseline = 7930 ± 314 vs R5-30 = 7150 ± 326, R35-60 = 6794 ± 349, and R65-90 = 6628 ± 311, P<0.05), while exercise at 50% of VO2peak caused no change, and exercise at 80% of VO2peak produced a significant increase at R5-30 (7468 ± 267 vs 9818 ± 366, P<0.05) and no change at R35-60 or R65-90. Cardiovascular responses were not altered during the control trial. In conclusion, varying exercise intensity from 30 to 80% of VO2peak in young normotensive humans did not influence the magnitude of post-exercise hypotension. However, in contrast to exercise at 50 and 80% of VO2peak, exercise at 30% of VO2peak decreased post-exercise HR and RP.

Developed pressure data may provide misinformation when used alone to evaluate systolic function in isovolumetric left ventricle preparations

We report data showing that developed pressure (DPmax) may lead to opposite conclusion with respect to maximal developed circumferential wall stress (smax) when used to assess contractile function in left ventricle isovolumic preparations. Isovolumetric left ventricle preparations of rats with cardiac hypertrophy (H; N = 10) induced by isoproterenol administration showed higher DPmax (174 ± 14 mmHg) than control (C; N = 8) animals (155 ± 12 mmHg) or rats with regression (R; N = 8) of hypertrophy (144 ± 11 mmHg). In contrast, the estimated smax for C (145 ± 26 kdynes/cm2) and R (133 ± 17 kdynes/cm2) was higher than for H (110 ± 13 kdynes/cm2). According to Laplace's law, the opposite results of DPmax and smax may depend on the increased mass/volume left ventricle ratio of the hypertrophied hearts, which favored pressure generation. These results clearly show that DPmax should be used with caution to analyze systolic function.

Altered heart rate and blood pressure variability in mice lacking the Mas protooncogene

Heart rate variability is a relevant predictor of cardiovascular risk in humans. A significant genetic influence on heart rate variability is suggested, although the genes involved are ill-defined. The Mas-protooncogene encodes a G-protein-coupled receptor with seven transmembrane domains highly expressed in testis and brain. Since this receptor is supposed to interact with the signaling of angiotensin II, which is an important regulator of cardiovascular homeostasis, heart rate and blood pressure were analyzed in Mas-deficient mice. Using a femoral catheter the blood pressure of mice was measured for a period of 30 min and 250 data values per second were recorded. The mean values and range of heart rate and blood pressure were then calculated. Neither heart rate nor blood pressure were significantly different between knockout mice and controls. However, high resolution recording of these parameters and analysis of the data by non-linear dynamics revealed significant alterations in cardiovascular variability in Mas-deficient animals. In particular, females showed a strong reduction of heart rate variability. Furthermore, the data showed an increased sympathetic tone in knockout animals of both genders. The marked alterations detected in Mas-deficient mice of both genders suggest that the Mas-protooncogene is an important determinant of heart rate and blood pressure variability.

Reflex control of arterial pressure and heart rate in short-term streptozotocin diabetic rats

Impaired baroreflex sensitivity in diabetes is well described and has been attributed to autonomic diabetic neuropathy. In the present study conducted on acute (10-20 days) streptozotocin (STZ)-induced diabetic rats we examined: 1) cardiac baroreflex sensitivity, assessed by the slope of the linear regression between phenylephrine- or sodium nitroprusside-induced changes in arterial pressure and reflex changes in heart rate (HR) in conscious rats; 2) aortic baroreceptor function by means of the relationship between systolic arterial pressure and aortic depressor nerve (ADN) activity, in anesthetized rats, and 3) bradycardia produced by electrical stimulation of the vagus nerve or by the iv injection of methacholine in anesthetized animals. Reflex bradycardia (-1.4 ± 0.1 vs -1.7 ± 0.1 bpm/mmHg) and tachycardia (-2.1 ± 0.3 vs -3.0 ± 0.2 bpm/mmHg) were reduced in the diabetic group. The gain of the ADN activity relationship was similar in control (1.7 ± 0.1% max/mmHg) and diabetic (1.5 ± 0.1% max/mmHg) animals. The HR response to vagal nerve stimulation with 16, 32 and 64 Hz was 13, 16 and 14% higher, respectively, than the response of STZ-treated rats. The HR response to increasing doses of methacholine was also higher in the diabetic group compared to control animals. Our results confirm the baroreflex dysfunction detected in previous studies on short-term diabetic rats. Moreover, the normal baroreceptor function and the altered HR responses to vagal stimulation or methacholine injection suggest that the efferent limb of the baroreflex is mainly responsible for baroreflex dysfunction in this model of diabetes.