Effects of growth hormone following chronic angiotensin-converting enzyme inhibition in chronic heart failure: their relation to infarct size.

Growth hormone (GH) has been attracted as a possible adjunctive treatment for severe heart failure. However, its treatment effects have been still controversial. To assess severity of basal cardiac disease states in which GH might be effective, we analyzed the relation of treatment effects of GH following chronic angiotensin-converting enzyme (ACE) inhibition on cardiac function and structures to infarct size in rat model of chronic heart failure after myocardial infarction. One day after coronary occlusion, rats were randomized to either an ACE inhibitor, temocapril (T) (80 mg/L in drinking water) or placebo for 12 weeks. The animals received concomitant recombinant human (rh) GH (2 mg/kg/day, SC) (T + GH) or vehicle during the final 2 weeks. Compared with the T group, the T + GH group with large MI had smaller increments of left ventricular (LV) dP/dt(max) (0 vs 17%) and cardiac output (9 vs 49%), less improvement of LV relaxation (tau) (-3 vs 29%) and systemic vascular resistance (8 vs 29%), and a greater increase in LV end-diastolic pressure (123 vs -5%) than did the T+GH group with moderate MI. In the T + GH group when compared with the T group, these functional alterations were associated with a 12% reduction in the LV capillary density and a 21% increase in hydroxyproline contents in rats with large MI, whereas a 12% increase in the density and similar collagen contents were found in rats with moderate MI. Thus, prominent beneficial cardiovascular effects of the additive short-term, high-dose GH to chronic high-dose ACE inhibition were obtained in rats with moderate MI, whereas little additional benefit or even detrimental effects of GH were found in rats with large MI. The present study may provide an insight into the therapeutic strategy of GH given late after MI in the presence of chronic ACE inhibition in congestive heart failure.

Increased sinusoidal pressure is associated with early liver weight gain in ischemia-reperfusion injury in isolated perfused rat liver.

BACKGROUND: Hepatic ischemia-reperfusion (I/R) is accompanied by liver weight gain and ascites formation. This could be caused by an increase in sinusoidal pressure, a determinant of hepatic transvascular fluid movement. We determined the role of sinusoidal pressure, assessed by triple vascular occlusion pressure (P(to)), in the I/R injury in isolated rat livers perfused with leukocyte-free diluted blood bivascularly via the portal vein and hepatic artery. MATERIALS AND METHODS: Ischemia was induced at room temperature by occlusion of either the inflow lines of the hepatic artery and portal vein (the open outflow group, n = 10) or both the inflow and the outflow (hepatic venous) lines (the closed outflow group, n = 10) for 1 h, followed by 1-h reperfusion in a recirculating manner. RESULTS: Liver weight in both groups increased biphasically after reperfusion; the initial peak occurred at 3 min and the second peak at 60 min. Immediately after reperfusion, P(to) peaked, followed by a gradual decline. The initial weight increase in groups combined was significantly and positively correlated with an increase in P(to) (r = 0.716, P = 0.0002), but the second peak was independent of P(to). Liver injury, assessed by perfusate levels of hepatic enzymes and reduced bile flow rate, was observed at 60 min after reperfusion in both groups. CONCLUSIONS: These findings suggest that increased sinusoidal pressure contributes to only the early liver weight gain after reperfusion in isolated perfused rat livers. The late weight gain may be presumably due to liver injury.

Echocardiographic diagnosis of subepicardial aneurysm ruptured into the right ventricle after inferior myocardial infarction.

A subepicardial aneurysm is a rare complication of myocardial infarction that sometimes causes a left to right shunt at the ventricular level. We report on echocardiographic observations in two recent cases of inferior myocardial infarction complicated by rupture of a subepicardial aneurysm into the right ventricle (RV). Two-dimensional and color flow Doppler images in several planes offered diagnostic characteristics of the lesion, including discontinuity of the myocardium at the neck of the aneurysm, a narrow neck relative to the diameter of the aneurysm, and a back and forth flow at the neck of the aneurysm. These techniques also provided new findings, such as a two-chambered structure of the aneurysm and a circular flow pattern within the inner aneurysmal cavity. In addition, color flow Doppler imaging showed multiple shunt flows from the aneurysm to the RV. Echocardiographically diagnosed abnormalities were verified by and successfully treated with surgery in both cases. In conclusion, echocardiography with color flow Doppler imaging may have the potential to diagnose the anatomic and hemodynamic condition of a subepicardial aneurysm.