Reversal of dyskinesis by increased end diastolic segment length in ischaemic-reperfused myocardium.

Persistent dyskinesis is universally observed after reperfusion of a severely ischaemic segment. Although inotropic stimulation shows a latent contractile reserve, it is not known whether this reserve can be recruited by increasing end diastolic segment length (local length-tension relation). To investigate this, six anaesthetised open chest dogs were placed on right heart bypass to increase end diastolic segment length independently of mean arterial pressure. Instantaneous left ventricular pressure-segment length relations and fractional systolic shortening were determined by sonomicrometry in the centre of the region perfused by the left anterior descending coronary artery during sequential increases in end diastolic segment length. Measurements were made before occlusion of the left anterior descending coronary artery, during 1 h of occlusion, and after 2 h of reperfusion. Before ischaemia, segmental shortening increased from 11.0(SEM 1.6)% to 23.5(1.5)% (p less than 0.05) as end diastolic segment length increased. Dyskinesis developed during occlusion of the left anterior descending coronary artery [12.1(2.6)% control v -7.2(1.6)% occlusion, p less than 0.05] and was present over the entire range of end diastolic segment lengths. Following reperfusion, segmental dyskinesis [-2.5(2.4)%] persisted at the lower end of the range of end diastolic segment length, but was progressively replaced by active shortening, averaging 7.3(3.2)% (p less than 0.05) as end diastolic segment length was sequentially increased. We conclude that segmental function following reperfusion is sensitive to changes in end diastolic segment length, and that active shortening is recruited from an apparently dyskinetic segment as end diastolic segment length progressively increases.

Adjuvant N-(2-mercaptopropionyl)-glycine in blood cardioplegia does not improve myocardial protection in ischemically damaged hearts.

Oxyradicals potentially limit the myocardial protection provided by blood cardioplegia in ischemically damaged hearts. We tested the hypothesis that the addition to blood cardioplegic solution of a new oxyradical scavenger--N-(2-mercaptopropionyl)-glycine--would result in improved left ventricular performance and oxygen consumption compared to that resulting from the use of blood cardioplegia alone. Gauges and transducer-tipped catheters for left ventricular minor axis ultrasonic dimension were placed in 17 open-chest dogs, and instantaneous left ventricular pressure-diameter data were acquired by computer. The aorta was crossclamped for 30 minutes during total vented bypass to induce ischemic injury. The heart was reoxygenated and protected by multidose, hypothermic blood cardioplegic solution alone (n = 9) or enhanced with 0.0132 mmol N-(2-mercaptopropionyl)-glycine (n = 8) for 1 hour of cardioplegia-induced arrest. Preischemic and postischemic left ventricular performance was measured by slope changes in end-systolic pressure-diameter relations induced by gradual afterload reduction during right heart bypass. When blood cardioplegia alone was used, postischemic left ventricular systolic performance was depressed by 73.2% +/- 10.0% (166.8 +/- 56.1 mm Hg/mm versus 25.1 +/- 7.0 mm Hg/mm). N-(2-mercaptopropionyl)-glycine did not significantly attenuate this functional depression (62.7% +/- 9.0%, 146.6 +/- 67.6 mm Hg/mm versus 33.6 +/- 11.9 mm Hg/mm). The postischemic end-diastolic pressure-diameter relation was shifted to the right, whereas chamber stiffness was increased comparably, with or without N-(2-mercaptopropionyl)-glycine. Postischemic oxygen consumption in the beating working state, calculated from left ventricular blood flow (measured by microspheres) and arterial-coronary sinus oxygen extraction, averaged 7.8 +/- 0.9 ml O2/100 gm/min with blood cardioplegia alone and 7.5 +/- 1.0 ml O2/100 gm/min with N-(2-mercaptopropionyl)-glycine, and was unchanged from paired preischemic values in both groups. We conclude (1) that N-(2-mercaptopropionyl)-glycine added to blood cardioplegic solution in the dose and delivery regimen tested did not improve ventricular systolic and diastolic performance compared with blood cardioplegia alone and (2) that postischemic oxygen consumption may not parallel the extent of left ventricular functional recovery.

Myocardial protection with blood cardioplegia in ischemically injured hearts: reduction of reoxygenation injury with allopurinol.

Myocellular injury mediated by oxygen radicals potentially limits myocardial protection in ischemically damaged hearts. This damage may be greater with oxygen-carrying blood cardioplegic solutions. A major mechanism of oxygen radical production is the conversion of hypoxanthine to uric acid by xanthine oxidase. In 16 anesthetized dogs, we studied whether adding allopurinol, a xanthine oxidase inhibitor, to blood cardioplegia would improve recovery of left ventricular (LV) performance and oxygen consumption. Millar transducer-tipped catheters and minor axis ultrasonic crystals were placed to assess LV performance by the slope of the end-systolic pressure-minor axis diameter relationships (Emax). Following total vented bypass, the hearts underwent 30 minutes of normothermic ischemia and then hypothermic blood cardioplegia with 1 mM allopurinol (N = 8) or without allopurinol (N = 8). Postischemic LV performance was significantly better with allopurinol than without (49.5 +/- 8.0 versus 17.4 +/- 4.1% of preischemic Emax; p less than 0.004). Postischemic LV oxygen consumption in the beating working state, calculated from LV blood flow (15 microm microspheres) and oxygen extraction, was comparable to preischemic values with and without allopurinol (10.2 +/- 1.2 versus 8.6 +/- 1.2 ml O2/100 gm/min). We conclude that allopurinol enhancement of blood cardioplegia increases myocardial protection in severely ischemic ventricles.

Oxygen-derived free radical scavengers and skeletal muscle ischemic/reperfusion injury.

Total injury in ischemic skeletal muscle is a function of ischemic damage and reperfusion injury. In an attempt to decrease reperfusion injury, we gave the oxygen-derived free radical scavengers allopurinol, superoxide dismutase, or mannitol during reperfusion of canine gracilis muscle made ischemic for 4 hours. We measured muscle O2 consumption (MVO2), and tissue calcium, water, and adenosine triphosphatase (ATP) before ischemia, after ischemia, and at 5 minutes and 60 minutes of reperfusion. The results at 60 minutes showed no improvement in MVO2 or ATP. In fact, ATP was significantly depressed with allopurinol and superoxide dismutase treatment, and tissue edema did not decrease in any of the groups. We conclude that the simple addition of oxygen-derived free radical scavengers during the initial reperfusion of totally ischemic skeletal muscle does not attenuate reperfusion injury.

Assessment of accuracy of intraesophageal pH probe in a dog model.

We performed an experiment in dogs in order to assess the accuracy of an intraesophageal pH probe and to examine possible mechanisms for any lack of accuracy. Two pH probes were placed in the esophagus of supine anesthetized dogs and acid was infused in small serial volumes from an infusion tube placed at the gastroesophageal junction. Two general patterns of pH probe responses were seen: (1) neither probe recorded a fall in pH with acid infusion, and (2) both probes recorded a fall in pH, but in a nonsynchronous manner. Changing the relationship of the tips of the probes with respect to the adjacent mucosa caused a fall in the pH recorded by each probe to the pH of the intraesophageal infusate. This and other evidence seen in the pH tracings suggest that mucosal abutment of the probe tips causes a falsely negative pH recording and raises the question of whether such a phenomenon occurs in human studies.