EFFECT OF ENDOGENOUS NITRIC-OXIDE ON CARDIAC SYSTOLIC AND DIASTOLIC FUNCTION DURING ISCHEMIA AND REPERFUSION IN THE RAT ISOLATED-PERFUSED HEART

Nitric oxide (NO) protects the heart against some forms of reperfusion -associated dysfunction (e.g. arrhythmias). Its role in protecting aga inst other types of dysfunction is controversial. NO ameliorates polym orphonuclear cell-induced exacerbation of stunning. Here, whether endo genous NO protects against contractile dysfunction in a polymorphonucl ear cell-free model has been tested. Isolated rat hearts (n = 6 per gr oup) were perfused with Krebs solution for 15 min. They were then perf used with test solution: Krebs, or Krebs containing 100 mu M N-G-nitro -L-arginine methyl ester (L-NAME) (a concentration shown previously to significantly reduce NO content in coronary effluent), 100 mu M L-NAM E plus 10 mM L-arginine (the latter shown previously to be sufficient to surmount the effect of L-NAME), or 10 mM L-arginine alone. After 10 min of this, the hearts were subjected to 60-min normothermic global ischemia followed by reperfusion with the same test solution as before , A time-matched (sham) group was perfused continuously with Krebs. L- NAME hastened the onset of ischemic contracture (P < 0.05) and increas ed its peak value from 67.8 +/- 4.6 mmHg to 93.0 +/- 4.9 mmHg (P < 0.0 5). Both effects were prevented by co-perfusion with 10 mna L-arginine . Initially, reperfusion exacerbated diastolic contracture, but diasto lic pressure at a constant ventricular volume fell from 112 +/- 27 mmH g to 73 +/- 19 mmHg between the 5th and 60th min of reperfusion in dru g-free hearts, indicative of recovery from diastolic stunning. This re covery was not exacerbated or lessened by perfusion with L-NAME or L-a rginine. Left ventricular developed pressure increased from 42 +/- 2 m mHg to 106 +/- 18 mmHg in controls between 5 and 30 min after the star t of reperfusion, the latter value being indistinguishable from that i n the sham group. At this time, the value in the L-NAME group was simi lar (78 +/- 18 mmHg). This indicated complete recovery from systolic s tunning in both groups 30 min after the start of reperfusion. However, earlier after the start of reperfusion there had been zero pressure d evelopment in the L-NAME group (P < 0.05 v the control group). This wa s associated with severe impairment of recovery of coronary now, e.g. of only 18% of the mean coronary now in controls 5 min after the start of reperfusion (P < 0.05). At 30 min after the start of reperfusion ( when systolic function had recovered in the L-NAME group), now recover y had increased in this group to 96% of the mean control values, The i mpairment in rates of recovery of systolic function and coronary flow in the L-NAME group were each prevented by co-perfusion with L-arginin e (P < 0.05). In conclusion, endogenous NO may delay the onset and red uce the magnitude of ischemic contracture but, despite this, appears n ot to facilitate early recovery from systolic and diastolic stunning a s a result of any direct action in the myocardium. The beneficial effe ct it does possess in this polymorphonuclear cell-free preparation is transient and results from mediation of rapid recovery of coronary flo w during reperfusion. (C) 1996 Academic Press Limited