The purpose of this study was to clarify the characteristics of improved ischemic tolerance induced by severe, short-term food restriction in isolated, perfused rat hearts. Male Wistar (8 week-old) rats were given a food intake equivalent to a 70% reduction on the food intake of ad-libitum fed rats for 11 days (FR group and AL group, respectively). After this period, hearts were isolated and perfused in the Langendorff mode, and subjected to 20 min of global ischemia followed by 30 min of reperfusion. Although the coronary flow rate in the FR group (63.0 +/- 3.1 ml/min/g dry weight) was higher than that in the AL group (47.1 +/- 1.3 ml/min/g dry weight) during preischemic perfusion, the lactate release into the coronary effluent and absolute values of +dP/dt and -dP/dt in the FR group (2422 +/- 161 and -1282 +/- 51) were inversely lower than in the AL group (2971 +/- 156 and -1538 +/- 74, respectively). An increase in ischemic contracture was suppressed in the FR group. Following reperfusion, cardiac function, high-energy phosphate content, and intracellular pH, as measured by 31P-nuclear magnetic resonance spectroscopy, had recovered to a much greater degree in the FR group than in the AL group. The serum T3 level was significantly lower in the FR group (2.7 +/- 0.1 pg/ml) than in the AL group (3.6 +/- 0.1 pg/ml), and the levels of triglycerides, free fatty acids, insulin, and glucose were also significantly lower in the FR group than in the AL group. The protein expressions of myocyte enhancer factor 2A, Na(+), K(+)-ATPase, and phospholamban in the cardiac tissue were higher in the FR group than in the AL group. These results suggested that severe, short-term food restriction improves ischemic tolerance in rat hearts via altered expression of functional proteins induced by low serum T3 levels, decreased coronary conductance, and change in metabolic flux.

A 48-year-old man with a history of hypertension and diabetes mellitus was hospitalized with sudden onset of severe chest pain. He was in cardiogenic shock with a systolic pressure of 60 mm Hg. His electrocardiogram (ECG) showed ST-segment elevation in the precordial leads suggestive of acute anteroseptal myocardial infarction. The ST-segment returned to baseline after the systolic blood pressure rose to 100 mm Hg with the administration of sympathomimetic agents. Aortography and transesophageal echocardiography demonstrated type A aortic dissection and aortic regurgitation. Aortography and short-axis transesophageal echocardiography showed during diastole almost complete collapse of the true lumen of the ascending aorta caused by the intimal flap. The patient underwent surgical repair of the aortic dissection and implantation of Palmaz stents in the carotid arteries. Decreased blood pressure and the presence of aortic regurgitation accelerated the collapse of the true lumen during diastole in the ascending aorta, resulting in functional obstruction of the left main coronary artery, which may have been related to ST-segment changes in this case.

Poly(ADP-ribose) polymerase (PARP), an enzyme that is important to the regulation of nuclear function, is activated by DNA strand breakage. In massive DNA damage, PARP is overactivated, exhausting nicotinamide adenine dinucleotide and leading to cell death. Recent studies have succeeded in reducing cellular damage in ischemia/reperfusion by inhibiting PARP. However, PARP plays an important part in the DNA repair system, and its inhibition may be hazardous in certain situations. We compared the short-time inhibition of PARP against continuous inhibition during ischemia/reperfusion using isolated rat hearts. The hearts were reperfused after 21 minutes of ischemia with a bolus injection of 3-aminobenzamide (3-AB) (10 mg/kg) followed by continuous 3-AB infusion (50 μM) for the whole reperfusion period or for the first 6 minutes or without 3-AB. At the end of reperfusion, contractile function, high-energy phosphate content, nicotinamide adenine dinucleotide content, and infarcted area were significantly preserved in the 3-AB 6-minute group. In the 3-AB continuous group, these advantages were not apparent. At the end of reperfusion, PARP cleavage had significantly proceeded in the 3-AB continuous group, indicating initiation of the apoptotic cascade. Thus, continuous PARP inhibition by 3-AB does not reduce reperfusion injury in the isolated rat heart, which may be because of acceleration of apoptosis.

Whereas activation of ATP-dependent potassium (KATP) channels greatly improves postischemic myocardial recovery, the final effector mechanism for KATP channel-induced cardioprotection remains elusive. RhoA is a GTPase that regulates a variety of cellular processes known to be involved with KATP channel cardioprotection. Our goal was to determine whether the activity of a key rhoA effector, rho kinase (ROCK), is required for KATP channel-induced cardioprotection. Four groups of perfused rat hearts were subjected to 36 min of zero-flow ischemia and 44 min of reperfusion with continuous measurements of mechanical function and 31P NMR high-energy phosphate data: 1) untreated, 2) pinacidil (10 μM) to activate KATP channels, 3) fasudil (15 μM) to inhibit ROCK, and 4) both fasudil and pinacidil. Pinacidil significantly improved postischemic mechanical recovery [39 ± 16 vs. 108 ± 4 mmHg left ventricular diastolic pressure (LVDP), untreated and pinacidil, respectively]. Fasudil did not affect reperfusion LVDP (41 ± 13 mmHg) but completely blocked the marked improvement in mechanical recovery that occurred with pinacidil treatment (54 ± 15 mmHg). Substantial attenuation of the postischemic energetic recovery was also observed. These data support the hypothesis that ROCK activity plays a role in KATP channel-induced cardioprotection.

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