Ventricular remodeling and diastolic myocardial dysfunction in rats submitted to protein-calorie malnutrition

The effects of protein-calorie malnutrition (PCM) on heart structure and function are not completely understood. We studied heart morphometric, functional, and biochemical characteristics in undernourished young Wistar rats. They were submitted to PCM from birth (undernourished group, UG). After 10 wk, left ventricle function was studied using a Langendorff preparation. The results were compared with age-matched rats fed ad libitum (control group, CG). The UG rats achieved 47% of the body weight and 44% of the left ventricular weight (LVW) of the CG. LVW-to-ventricular volume ratio was smaller and myocardial hydroxyproline concentration was higher in the UG. Left ventricular systolic function was not affected by the PCM protocol. The myocardial stiffness constant was greater in the UG, whereas the end-diastolic pressure-volume relationship was not altered. In conclusion, the heart is not spared from the adverse effects of PCM. There is a geometric alteration in the left ventricle with preserved ventricular compliance despite the increased passive myocardial stiffness. The systolic function is preserved.

Effects of isoflurane on Tei-index of myocardial performance in healthy dogs

Recently, the Tei-index, a noninvasive index that combines systolic and diastolic time intervals, has been proposed to assess global cardiac performance. However, the effects of isoflurane on the Tei-index have not been characterized. This study aimed at studying the effects of 1.0 minimal alveolar concentration isoflurane anesthesia on the pre-ejection period (PEP), left ventricular ejection time (LVET), PEP/LVET ratio, isovolumic relaxation time (IVRT), stroke index (SI), cardiac index (CI), heart rate (HR), and the Tei-index in healthy unpremedicated dogs. We observed significant increases in PEP, PEP/LVET ratio, IVRT, and TEI, whose maximal increases obtained throughout the study were 47%, 48%, 78%, and 56%, respectively. The LVET and HR did not change significantly, whereas the SI and CI decreased during anesthesia (29% and 26%, respectively). In conclusion, isoflurane produced direct effects on the Tei-index. The changes in systolic and diastolic parameters were supportive of this finding and were consistent with an overall impairment of left ventricular function during anesthesia.

Doxorubicin as an antioxidant: Maintenance of myocardial levels of lycopene under doxorubicin treatment

The mechanism of doxorubicin-induced cardiotoxicity remains controversial. Wistar rats (n=96) were randomly assigned to a control (C), lycopene (L), doxorubicin (D), or doxorubicin+lycopene (DL) group. The L and DL groups received lycopene (5 mg/kg body wt/day by gavage) for 7 weeks. The D and DL groups received doxombicin (4 mg/kg body wt intraperitoneally) at 3, 4, 5, and 6 weeks and were killed at 7 weeks for analyses. Myocardial tissue lycopene levels and total antioxidant performance (TAP) were analyzed by HPLC and fluorometry, respectively. Lycopene metabolism was determined by incubating H-2(10)-lycopene with intestinal mucosa postmitochondrial fraction and lipoxygenase and analyzed with HPLC and APCI mass spectroscopy. Myocardial tissue lycopene levels in DL and L were similar. TAP adjusted for tissue protein were higher in myocardium of D than those of C (P=0.002). Lycopene metabolism study identified a lower oxidative cleavage of lycopene in D as compared to those of C. Our results showed that lycopene was not depleted in myocardium of lycopene-supplemented rats treated with doxorubicin and that higher antioxidant capacity in myocardium and less oxidative cleavage of lycopene in intestinal mucosa of doxorubicin-treated rats suggest an antioxidant role of doxombicin rather than acting as a prooxidant. (c) 2007 Elsevier B.V. All rights reserved.

Factors affecting metabolic and electrolyte changes after reperfusion in liver transplantation

Background. The metabolic and electrolyte changes were evaluated after various durations of cold and warm ischemia times to correlate ASA status with hemodynamic changes that may affect the severity of the reperfusion syndrome.Patients and methods. Sixty-one patients who underwent liver transplantation (OLT) were monitored by arterial pH, PaO2, PaCO2, HCO3, BE, K+, Ca2+, Na+, GL, and serial Ht at three specific times: after the skin incision (baseline), 10 minutes before reperfusion (T-2), and 10 minutes after reperfusion (T-3). Changes in metabolic parameters were correlated with ASA status, hemodynamic changes, time of OLT, as well as cold and warm ischemia times.Results. The pH in ASA IV patients was significantly lower at T-1 and T-3, and PCO2 higher in ASA V at T-1. A significant correlation was observed between pH, PaCO2, HCO3 BE, Na+, Ca2+, and glucose with the phase of the procedure. The pH and HCO3 decreased significantly from T-1 and T-2, increasing during T-3. Ca2+ fell from T-1 to T-2 increasing in T-3. Mean glucose and sodium levels increase from T-1 to T-3. Mean BE dropped from T-1 to T-2 and increased at T-3 without a significant correlation between the metabolic parameters in any phase of the study and the cold or warm ischemia times. Patients with a high ASA status showed an increased risk for cardiovascular collapse after reperfusion.Conclusions. Patients with advanced ASA status are more prone to metabolic and acid-base disturbances during reperfusion, without any relation to the cold or warm ischemia times. High ASA status shows an increased risk for cardiovascular collapse after reperfusion.

FTY720 prevents renal T-Cell infiltration after ischemia/reperfusion injury

Ischemia/reperfusion (I/R) injury, a common early feature in renal transplantation, results from both free radical species generation and local inflammatory responses that attract different types of cells. The interaction with infiltrating leukocytes could promote damage and death of resident renal cells contributing to worsening of renal function. It has been shown that depletion of host T cells protects against kidney damage after I/R injury, although the mechanism is not fully understood. FTY720, a synthetic analog of a natural product extracted from Isaria sincclairii has shown modulatory properties in experimental models of autoimmune disease, transplantation, and I/R injury. FTY720 alters lymphocyte responses to chemokine homing signals, thereby decreasing the number of lymphocytes in inflammatory sites. We evaluated renal function in mice at 3, 5, and 7 days after I/R injury in the presence or absence of FTY720 treatment. FTY720 treatment promoted earlier recovery of renal function associated with a lower number of renal-infiltrating lymphocytes. These findings confirm previous results showing a protective effect of FTY720 in I/R injury models.

Myocardial function during chronic food restriction in isolated hypertrophied cardiac muscle

Background: the effect of food restriction (FR) on myocardial performance has been studied in normal hearts. Few experiments analyzed the effects of undernutrition on hearts subjected to cardiac overload. The aim of this study was to determine whether chronic FR promotes more significant changes in hypertrophied hearts than in normal hearts. Methods: Myocardial performance was studied in isolated left ventricular papillary muscle from young male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) submitted to FR or to control diet. The animals subjected to FR were fed 50% of the amount of food consumed by control groups for 60 days. Isolated muscles were studied while contracting isometrically and isotonically. Results: FR decreased the body weight and the left ventricular weight in both groups. FR increased the left ventricular weight-to-body weight ratio in the WKY rats and tended to decrease this ratio in SHR (P = 0.055). The arterial systolic pressure was greater in SHR than in WKY groups and did not change with FR. In the animals with normal diet, myocardial performance was better in SHR than in WKY. FR increased time to tension to fall from peak to 50% of peak tension and time to peak tension in the WKY rats and time to peak tension in the SHR. Conclusions: FR for 60 days has a trend to attenuate the development of cardiac hypertrophy and does not promote more mechanical functional changes in the hypertrophied myocardium than in the normal cardiac muscle.

Improved systolic ventricular function with normal myocardial mechanics in compensated cardiac hypertrophy

There is still controversy about the relation between changes in myocardial contractile function and global left ventricular (LV) performance during stable concentric hypertrophy. To clarify this, we analyzed LV function in vivo and myocardial mechanics in vitro in rats with pressure overload-induced cardiac hypertrophy. Male Wistar rats (70 g) Underwent ascending aortic stenosis for 8 weeks (group AAS, n = 9). LV performance wits assessed by transthoracic echocardiography Under anesthesia. Myocardial function Was studied in isolated papillary muscle preparations during isometric contraction. The data were compared with age- and sex-matched sham-operated rats (group C, 11 = 9). LV weight-to-body weight ratio (C: 2.13 +/- 0.14 mg/g; AAS: 3.24 +/- 0.44) LV relative wall thickness (C: 0.18 +/- 0.02; AAS: 0.33 +/- 0.09), and LV fractional shortening (C: 54 +/- 5%; AAS: 70 +/- 8%) were increased in group AAS (P<0.05). Echocardio-graphic analysis also indicated a significant association (r = 0.74 P<0.001) between the percent fractional shortening index and LV relative wall thickness. The performance of AAS isolated In muscle revealed that active tension (C: 6.6 +/- 1.7 g/mm(2); AAS: 6.5 +/- 1.5 g/mm(2)) and maximum rate of tension development (C: 69 +/- 21 g/mm(2)/s AAS: 69 +/- 18 g/mm(2)/s) were not significantly different Front group C (P>0.05). In conclusion, compensated pressure-overload myocardial hypertrophy is associated with preserved myocardial function and increased ventricular performance. The improved LV function might be due to the ventricular remodeling, characterized by an increased relative wall thickness.