Is warm retrograde blood cardioplegia better than cold for myocardial protection?

BACKGROUND: This study tests the hypothesis that continuous normothermic retrograde blood cardioplegia is superior to cold intermittent blood cardioplegia in protecting the left and right side of the heart transmurally during an extended cross-clamping period. METHODS: Twelve anesthetized, open chest dogs were placed on cardiopulmonary bypass and randomized to receive continuous warm (n = 6) or intermittent cold cardioprotection (n = 6) during a 3-hour aortic cross-clamp period. Transmural left ventricular muscle biopsy specimens were taken before the initiation of cardiopulmonary bypass and 90 and 180 minutes after cross-clamping. Right ventricular (RV) biopsy specimens were taken 180 minutes after aortic cross-clamping. Biopsy specimens were analyzed for adenosine triphosphate, creatine phosphate, and lactate levels and for morphologic changes via electron microscopy. RESULTS: At the end of 180 minutes of cardiopulmonary bypass, the adenosine triphosphate contents of endocardial and epicardial halves of the left ventricular myocardium were only slightly degraded in both cardioplegia groups; a significantly greater reduction in adenosine triphosphate levels occurred in the RV of the warm compared with the cold group (p < 0.02). The difference in creatine phosphate values in the left ventricle between the cold group (35.2 +/- 23.4 nmol/mg cardiac protein) and the warm animals (64.4 +/- 24.9 nmol/mg cardiac protein) was not statistically significant, but the RV creatine phosphate stores were significantly better preserved in the warm compared with the cold cardioplegia group (p < 0.02). Lactate levels increased to a similar extent in both groups, but both values rose significantly over baseline (p < 0.03). Importantly the electron microscopic score of the left ventricle and RV indicated that cells were reversibly and not irreversibly damaged with both cardioplegic protections. CONCLUSIONS: These results suggest the following: (1) Chemical arrest is a major contributor of myocardial preservation during diastolic arrest as used in clinical cardiac surgery. (2) Both methods preserve the ultrastructure of the myocytes transmurally during 3 hours of aortic cross-clamping. (3) Both techniques protect the RV and left ventricle; however, to provide optimal protection of the RV, alternated retrograde and antegrade perfusion might be beneficial over retrograde cardioplegia flow alone, in particular with warm cardioplegia.

Do antioxidant vitamins reduce infarct size following acute myocardial ischemia/reperfusion?

There is controversy concerning the ability of antioxidant vitamins to reduce myocardial infarct size. We sought to determine whether a brief prophylactic treatment of vitamin C or vitamin C plus Trolox (a water-soluble form of vitamin E) could reduce myocardial infarct size in an experimental model. We used an anesthetized open-chest rabbit model in which a branch of the circumflex coronary artery was ligated for 30 minutes followed by 4 hours of reperfusion. Experiments were performed in a randomized and blinded fashion. An IV injection of normal saline pH balanced to 7.4 (control group n = 15), vitamin C (150 mg/kg, n = 14), or vitamin C plus Trolox (150 mg/kg plus 100 mg/kg, respectively, n = 15) was administered prior to coronary occlusion. Collateral blood flow during coronary occlusion was measured by radioactive microspheres, myocardial risk zone (AR) was assessed by blue dye injection, and myocardial infarct size (AN) was assessed by triphenyltetrazolium chloride staining. All rabbits received comparable ischemic insult: Collateral blood flow and AR were similar among all three groups. Infarct size, measured as a percent of AR, did not differ significantly among the controls (21%), vitamin C (29%), or the vitamin C plus Trolox (18%) groups. Therefore, in this ischemia/reperfusion model, antioxidant vitamins did not alter myocardial infarct size.

An adenosine A1 receptor agonist, R(-)-N-(2-phenylisopropyl)-adenosine (PIA), but not adenosine itself, acts as a therapeutic preconditioning-mimetic agent in rabbits.

OBJECTIVE: A preconditioning mimetic agent could be useful therapy for cardiac ischaemic events; stimulation of adenosine receptors has been proposed as a preconditioning mediator. The ability of adenosine-receptor activation to mimic ischaemic preconditioning was tested in an in vivo rabbit model. METHODS: Adenosine (15 mg, a maximally tolerated dose, n = 10) was infused over six minutes via a coronary artery and compared with saline (n = 12) in anaesthetised rabbits. Five minutes after infusion, a coronary artery was occluded for 40 minutes followed by three hours of reperfusion. In a second study, preischaemic intravenous treatment with adenosine (25 mg.kg-1, n = 9), or an A1-adenosine agonist, R(-)-N-(2-phenylisopropyl)-adenosine (PIA, 900 micrograms.kg-1, n = 12), were compared with saline (n = 12), when given before 40 minutes of coronary artery ligation and three hours of reperfusion in anaesthetised rabbits. RESULTS: Intracoronary adenosine reduced mean arterial pressure during infusion (48(3) v 80(4) mm Hg, control, p < 0.001); however, infusion regional myocardial blood flow was significantly higher in adenosine treated hearts (5.00(0.90) v 2.30(0.26) ml.min-1 x g-1, p < 0.02) in the region later to become ischaemic. During occlusion ischaemic blood flow was similar in both groups as was the size of the ischaemic risk region, expressed as a % of the left ventricle (42(3)% adenosine and 37(3)% control, NS). Intracoronary adenosine treatment failed to reduce infarct size (52(5)% of the risk zone v 57(7)% in controls, NS). In the second protocol, heart rate immediately after treatment was reduced by both intravenous denosine (26%) and PIA (22%) v control, indicating atrial A1 receptor activation. Treatment with PIA resulted in a significant reduction in ultimate infarct size compared with saline (38(5)% of risk region v 57(5)%, p < 0.05). Adenosine, however, failed to reduce infarct size (50(8)%, NS v saline). There were no differences between area at risk or myocardial blood flow among groups. CONCLUSION: The adenosine agonist PIA but not adenosine itself might be a useful adjunctive therapy.