METABOLIC ABNORMALITIES AND DIFFERENTIAL RESPONSES TO STRESS ASSOCIATED WITH HAMSTER CARDIOMYOPATHY

Metabolic differences between cardiomyopathic hamsters (CMHs), as they progress through Various physiologic phases before reaching end-stage heart failure (HF), and healthy hamsters (HHs) are often difficult to demonstrate. We suggest that metabolic differences, magnified by appl ication of chronic stress (S: cold immobilization 2 hr/day for 5 days) followed by acute stress (AS: 55 min global ischemia /30 min reperfus ion), can be used to characterize different stages in this cardiomyopa thic process, High performance liquid chromatography (HPLC) and P-31 N MR methods were used to monitor the effects of acute stress applied to nonstressed (NS) and previously stressed CMHs (NS-2.5-month NS-5-mont h; S-2.5-month, S-5-month) and HHs(NS-HH,S-HH). Cardiac tissue extract s from nonstressed and stressed hamsters were analyzed for ATP and PCr at baseline and after completion of ischemia/reperfusion (AS) using H PLC. In nonstressed hamsters, ATP and PCr were 12% lower in CMHs (both NS-2.5- and NS-5-month) than in NS-HHs, After exposure to stress, ATP was 26% lower in CMHs (S-2.5- and S-5-month) compared to S-HHs, where as there were minimal differences in PCr between the groups, P-31 NMR monitoring of metabolism in the perfused beating heart during applicat ion of acute stress produced similar changes (%) in ATP and PCr in all groups (NS and S), whereas P-1 increase was less in NS-5-month (118%) compared to NS-2.5-month (179%) and NS-HHs (306.8%), P < 0.05; and in S-5-month (148%) compared to S-2.5-month (216%) and S-HHs (222%). The changes in myocardial pH were inversely related to changes in P-i: NS -5-month (-13.5%); NS-2.5-month (-9.7%); NS-HH (-17.7%). pH changes in stressed cardiomyopathic hamsters were similar to those of S-HHs. The postischemic recovery of ATP and P, return closer to baseline values in cardiomyopathic hamsters (both NS and S) compared to healthy hamste rs. The data suggest that cardiomyopathic hamsters have baseline metab olic abnormalities, and their responses to chronic cold immobilization stress, acute ischemia, and chronic cold immobilization stress plus a cute ischemia are different from those in HHs, These responses may hel p to characterize specific stages of disease.