Do overlapping vessels protect against canine right ventricular infarction after right coronary artery occlusion?

The severity of ischaemia in the left ventricle from total coronary occlusion is modified by retrograde blood flow through collateral or overlapping vessels, but whether that is true for the right ventricle is not known. The consequences and extent of ischaemic damage from occlusion of the right coronary artery were studied in anaesthetised dogs. In group 1 (n = 9), the right coronary artery alone was occluded; in group 2 (n = 8), the right coronary artery and overlapping vessels from the left anterior descending and circumflex coronary arteries were occluded. Occlusion for 2 h caused right ventricular end diastolic pressure to increase by 2.8(SEM 0.4) mm Hg in group 1 (p less than 0.05) and by 1.9(0.5) mm Hg in group 2 (p less than 0.05). Fractional shortening in the ischaemic zone became akinetic in group 1: 12.0(1.4)% v 0.1(1.6)%; p less than 0.05; and dyskinetic in group 2: 12.1(2.1)% v -1.2(0.9)%; p less than 0.05. In both groups, fractional shortening remained depressed during the ensuing 2 h of reperfusion. The incidence of right ventricular free wall necrosis was 56% in group 1 but 100% in group 2 (p = 0.082). The area of necrosis, expressed as a percentage of the area at risk, was 13.9(6.6)% in group 1 in contrast to 66.9(4.5)% in group 2 (p less than 0.05). Both groups had equal involvement of the subendocardial and subepicardial layers. We conclude that ligating epicardial overlapping vessels in addition to the right coronary artery produces a larger area of right ventricular free wall necrosis.

Differential effects of positive end expiratory pressure and cardiac tamponade on left-right ventricular mechanical function in the dog.

OBJECTIVE: The aim was to examine the hypothesis that an increased coupling occurs between the ventricles during tamponade via a ventricular-pericardial-ventricular interaction, but that ventricular coupling would be unaltered or reduced with positive end expiratory pressure (PEEP). METHODS: An in situ arrested, canine heart preparation was used. Changes in left and right ventricular pressure (dPl, dPr) and volume (dVl, dVr) caused by increasing the volume of the other ventricle were measured at normal and at matched levels of raised pericardial pressures (Pp) caused by 20 cm H2O PEEP and by tamponade. RESULTS: With PEEP, the coupling between the ventricles was unaltered when compared to control. With tamponade, dPl/dPr, dVl/dPr, dPr/dPl, and dVr/dPl increased significantly (p less than 0.05) by 0.21 (SEM 0.03, unitless), 0.45(0.04) ml.mm Hg-1, 0.18(0.03), and 0.28(0.04) ml.mm Hg-1 respectively. CONCLUSIONS: Augmented ventricular interdependence occurs during tamponade but not with PEEP, which may help to explain the different haemodynamic patterns observed under these conditions.

Effects of increased pericardial pressure on the coupling between the ventricles.

STUDY OBJECTIVE: The mechanical coupling between the ventricles occurs directly through the myocardium (ventricular-ventricular coupling) and indirectly through the pericardium (ventricular-pericardial-ventricular coupling). We postulated that the magnitude of ventricular-pericardial-ventricular coupling would increase at high pericardial pressures, while ventricular-ventricular coupling would be unaltered. DESIGN: Canine hearts were removed and placed in cold cardioplegic solution. Balloons were inserted into each ventricle and the left and right ventricular pressure (dP1, dPr) and volume (dV1, dVr) changes caused by increasing the pressure and volume of the other ventricle and by increasing pericardial pressure (dPp) were measured. EXPERIMENTAL MATERIALS: Hearts from 10 random source dogs, weight 12.5-18 kg, were used. MEASUREMENT AND MAIN RESULTS: At control pericardial pressure levels, the magnitude of the pericardial-ventricular interactions was greater than the ventricular-ventricular interactions: dP1/dPp was significantly greater than dP1/dPr, at 0.71 (SEM 0.04), n = 6, v 0.18 (0.03), p less than 0.01, and dV1/dPp was significantly greater than dV1/dPr, at -0.83 (0.09) v -0.24 (0.06), p less than 0.05. Raising the pericardial pressure increased the mechanical coupling between the ventricles: dP1/dPr approximately, dV1/dPr approximately, dPr/dP1 approximately, and dVr/dP1 approximately increased significantly (p less than 0.05) by 0.48 (0.03), 0.67 (0.13), 0.38 (0.05), and 0.61 (0.09) respectively. This increased coupling occurred through pericardial pressure changes. If pericardial pressure was maintained constant, the coupling between the ventricles was unaltered. This same pattern was observed in four in situ experiments. For these experiments, at the raised pericardial pressure levels, dP1/dPr increased, from 0.51 (0.03) to 0.79 (0.01), p less than 0.05, if pericardial pressure was allowed to vary, but was unaltered with a constant pericardial pressure, at 0.42 (0.03) v 0.44 (0.04), p greater than 0.5. CONCLUSIONS: Ventricular interdependence was increased with raised pericardial pressure and this increased coupling was due primarily to an increased ventricular-pericardial-ventricular coupling. This increased coupling may help to explain the paradoxical pulse observed in cardiac tamponade.

Alterations in left ventricular compliance due to changes in right ventricular volume, pressure and compliance.

Because of ventricular interdependence, part of the measured left ventricular diastolic pressure can be attributed to the right ventricle. Therefore, we examined the hypothesis that left ventricular diastolic properties are modified by alterations in right ventricular compliance and pressure even without a change in right ventricular volume. To examine this hypothesis, the hearts were removed from six dogs, the coronary arteries perfused with cool cardioplegic solution, and the hearts submerged in cool cardioplegic solution. Balloons were inserted into each ventricle. Left ventricular pressure-volume curves were recorded and approximated by an exponential equation. With no fluid in the right ventricular balloon (control), the exponential coefficient and constant were 0.038 (SD 0.004) ml-1 and 2.38(0.75) mm Hg respectively. With right ventricular pressure held constant at 20 mm Hg, the exponential coefficient and constant were 0.035(0.002) ml-1 and 3.71(1.64) mm Hg (p less than 0.05 v control constant), respectively. With a fixed right ventricular volume, the exponential coefficient and constant were significantly different (p less than 0.05 v control values) at 0.040(0.006) ml-1 and 2.81(0.96) mm Hg, respectively. After decreasing right ventricular free wall compliance by injecting glutaraldehyde into the right coronary artery, the exponential coefficient and constant were significantly different (p less than 0.01 v control values) at 0.058(0.010) ml-1 and 1.86(0.60) mm Hg, respectively. Thus, even with a constant right ventricular pressure or volume, a significant upward shift in the left ventricular pressure-volume relation occurred. Decreasing right ventricular free wall compliance further increased left ventricular pressure. The results of these studies indicate that the diastolic properties of the left ventricle can be modified by changes in right ventricular pressure and compliance even without a change right ventricular volume. Thus indices of left ventricular diastolic properties may be altered by changes in the characteristics of the right ventricle.

Variable non-linearity in end systolic pressure-volume relationships results from interaction between end diastolic and developed pressure-volume relations.

OBJECTIVE: The aim was to determine the contributions of diastolic pressure to the shape of the relationship of total systolic left ventricular pressure with volume (pressure-volume relationship). STUDY DESIGN: The pressure-volume relationship was approximated (by least squares fit) to a parabola P = aV2 + bV + C. Non-linearity was indicated by values "a" significantly different from zero. Negative values indicated concavity to the volume axis, positive values convexity to the volume axis. MATERIALS: Langendorff perfused rabbit hearts (n = 8) with intraventricular balloon were used. Balloon pressure was measured for varying balloon volumes. RESULTS: The total systolic pressure-volume relationship was concave towards the volume axis at 2.4 mM extracellular calcium ions concentrations ([Cae++]) a = -47.2 (SD 5.4), p less than 0.05. It was nearly linear at [Cae++] = 0.6 mM; a = -0.8(5.8), p greater than 0.05. It was convex at [Cae++] = 0.3 mM; a = 25.3(4.0), p less than 0.01. The diastolic pressure-volume relationship was always convex: a = 30.1(6.7), 33.5(7.6), 42.2(6.6) for [Cae++] = 2.4, 0.6, and 0.3 mM respectively. When these diastolic values were subtracted from the total pressures, pressure-volume curves for developed pressure were obtained which were always concave: a = -76.9(10.2), -33.5(3.7), -16.3(2.9) for [Cae++] = 2.4, 0.6, and 0.3 mM. CONCLUSIONS: The true systolic pressure-volume relationship of the left ventricle is not linear but concave to the volume axis. The slope is therefore variable and not an index of contractility. Apparently linearity or convexity is due to inappropriate addition of the diastolic pressure-volume properties.

Effect of acute cardiac tamponade on left ventricular pressure-volume relations in anaesthetised dogs.

STUDY OBJECTIVE: The aim was to determine whether depressed myocardial contractility is responsible for the decline in stroke volume that occurs with cardiac tamponade. DESIGN: Left ventricular contractile performance was assessed before and after beta adrenergic blockade using the end systolic pressure-volume relation, the left ventricular dP/dtmax-end diastolic volume relation, and the left ventricular stroke work-end diastolic volume relation during acute cardiac tamponade in dogs. EXPERIMENTAL MATERIAL: In eight pentobarbitone anaesthetised dogs (15.7-24.8 kg), transducer tipped and volume impedance catheters were positioned in the left ventricle. Through a median sternotomy incision, a pericardial catheter was inserted to produce varying stages of cardiac tamponade. By the use of transient bicaval occlusions, variably loaded pressure-volume loops were recorded. MEASUREMENTS AND RESULTS: Incremental tamponade reduced mean arterial pressure from 105(SEM 3) to 89(2) mm Hg (mild tamponade), 75(2) mm Hg (moderate tamponade), and 59(10) mm Hg (severe tamponade). The slope of the end systolic pressure-volume relation was 6.3(1.2) mm Hg.ml-1 at baseline and increased slightly to 7.7(1.8), 8.5(1.3), and 9.2(1.5) mm Hg.ml-1 with the progressive levels of tamponade (NS). The role of autonomic reflexes was assessed by repeating the tamponade sequence after beta adrenergic blockade with 10 mg of metoprolol intravenously. The slope of the end systolic pressure-volume relation was reduced by metoprolol, at 4.9(1.0) mm Hg.ml-1 (p less than 0.01), but was not significantly altered by the sequence of tamponade following beta blockade [5.6(0.9), 6.0(1.0), and 5.5(7.0) mm Hg.ml-1, respectively (NS)]. Neither were changes found indicative of depressed contractile function with progressive tamponade in the slopes of the left ventricular dP/dtmax-end diastolic volume and stroke work-end diastolic volume relations. CONCLUSIONS: Left ventricular contractility was not altered during acute cardiac tamponade in an anaesthetised, closed chest canine model. Depressed left ventricular contractile function was not responsible for the observed haemodynamic deterioration.

Protection from ischaemic-reperfusion injury with adenosine pretreatment is reversed by inhibition of ATP sensitive potassium channels.

OBJECTIVE: The aim was to test the hypothesis that the cardioprotective effects against ischaemic-reperfusion injury of pretreatment with adenosine are mediated in part by activation of ATP sensitive potassium channels (K+ATP channels). METHODS: 42 anaesthetised New Zealand White rabbits underwent 30 min coronary occlusion, followed by 2 h reperfusion. Half the animals received a 5 min infusion of 140 micrograms.kg-1.min-1 of adenosine as pretreatment. The remainder of the animals received a 5 min infusion of saline alone as pretreatment. Animals pretreated with adenosine received either a low dose of the K+ATP channel blocker glibenclamide (0.3 mg.kg-1), high dose glibenclamide (3.0 mg.kg-1), or vehicle immediately prior to ischaemia to test whether glibenclamide can reverse the protective effects of adenosine, thus allowing the adenosine effect but antagonising K(+)ATP channel activation during ischaemia. Animals which received saline pretreatment also received low dose glibenclamide, high dose glibenclamide, or vehicle (controls) to evaluate the effect of glibenclamide alone. Infarct size was determined with tetrazolium and Unisperse Blue stains, and transmural blood flow was measured using radioactive microspheres. RESULTS: Although there were no differences in collateral myocardial blood flow during ischaemia or in risk area among the groups, infarct size was reduced by adenosine pretreatment to 8 (SEM 3)% v 36(4)% in controls (p < 0.05). K(+)ATP channel blockade with low dose glibenclamide in saline pretreated animals did not by itself extend the degree of necrosis [33(4)%], whereas low dose glibenclamide prevented the protective effects of adenosine pretreatment [38(3)%]. High dose glibenclamide reversed adenosine protection as well [54(3)%], but at a dose which increased infarct size in saline pretreated animals [52(3)%]. CONCLUSIONS: While adenosine pretreatment protects against necrosis in the rabbit, (1) the expression of this protection depends at least in part upon the actions of K(+)ATP channels during ischaemia, and (2) glibenclamide at higher doses increases infarct size, suggesting either that the K(+)ATP channel is endogenously protective during ischaemia, or that the higher dose has other infarct extending effects.

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.

Validation of local venous sampling within the at risk left anterior descending artery vascular bed in the canine left ventricle.

The validity of using blood sampled from the anterior interventricular vein (AIV), anatomically located within the myocardium perfused by the left anterior descending (LAD) coronary artery, to represent venous drainage originating from the LAD vascular territory was studied in eight anaesthetised, open chest dogs. The LAD was cannulated and perfused from a blood reservoir isolated from the systemic circulation. To determine the presence of blood from non-LAD sources that appears in the AIV sample, 51Cr-labelled red blood cells were injected into the left atrium and distributed in the systemic circulation while the LAD was perfused by non-radioactive blood. The percentage spillover of red blood cells from non-LAD sources into the AIV drainage was determined under control, reduced LAD flow, ischaemia, and reperfusion conditions as 100 X (AIV chromium content/arterial chromium content). Spillover of red blood cells into AIV blood samples averaged only 1.5(1.3)% under control conditions and increased insignificantly to 8.6(3.5)% during reduced LAD flow. During ischaemia red blood cells in AIV blood increased insignificantly to 98.3(5.0)% but decreased to 1.9(1.3)% after reperfusion. Studies in five dogs with microspheres showed that a portion of this admixture from non-LAD sources originated from precapillary nutritional collateral or overlapping blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume expansion increases right ventricular infarct size in dogs by reducing collateral perfusion.

STUDY OBJECTIVE: Plasma volume expansion is frequently recommended to correct the low output state resulting from right ventricular (RV) infarction. However, any subsequent increase in pericardial and RV filling pressures from volume expansion could impair RV collateral blood flow. We examined whether volume expansion in dogs before right coronary ligation reduced collateral perfusion and worsened the extent of RV necrosis. DESIGN: Randomized experimental study. SETTING: Animal research laboratory in university medical center. PARTICIPANTS: Forty anesthetized, closed-chest dogs were randomly assigned to normovolemic, pericardium opened (n = 10) or intact (n = 10) groups, and hypervolemic, pericardium opened (n = 10) or intact (n = 10) groups. INTERVENTIONS: Hypervolemic animals received 24 mL/kg of 6% hetastarch. All animals underwent 90 min right coronary ligation, followed by 120 min reperfusion. Collateral coronary blood flow (radioactive microspheres) and area of necrosis (An) were determined in the area at risk (Ar). MEASUREMENTS AND RESULTS: Stroke volume decreased in all groups with ischemia but remained 25 to 40% greater in both hypervolemic groups than in normovolemic animals (p < 0.05). In hypervolemic animals with intact pericardium, RV end-diastolic pressure increased to 10.4 +/- 2.1 mm Hg (mean +/- SD), a value that significantly exceeded those of the other three groups. During RV ischemia, collateral perfusion in the Ar was similar in both normovolemic groups and in hypervolemic animals with opened pericardium (mean range, 12.9 +/- 8.8 to 13.8 +/- 7.6 mL/min/100 g; p = NS), and the An/Ar varied from 11.8 +/- 6.3 to 18.6 +/- 17.4% (p = NS). In contrast, in hypervolemic animals with intact pericardium, collateral perfusion decreased to 7.2 +/- 3.5 mL/min/100 g and the An/Ar was increased to 38.2 +/- 18.6% (p < 0.05 compared with other groups, respectively). Overall, An/Ar was inversely related to collateral blood flow in the Ar (r = -0.46; p < 0.05) and correlated positively with RV end-diastolic pressure (r = 0.61; p < 0.05). CONCLUSIONS: Volume expansion preserved stroke volume during RV ischemia, independent of pericardial integrity. However, volume expansion in animals with an intact pericardium increased RV infarct size by twofold to threefold secondary to reduced periischemic collateral perfusion. This detrimental effect of volume expansion on infarct size was prevented by opening the pericardium.

Reperfusion injury after temporary coronary occlusion.

In 24 anesthetized open-chest dogs, we examined the time course of changes in contractile function, diastolic muscle stiffness (sonomicrometry), tissue water content, and ultrastructure after 1 hour of occlusion of the left anterior descending coronary artery and after 2 hours of unmodified reperfusion. One hour of occlusion of the left anterior descending artery replaced active shortening with passive bulging (21.4% +/- 2.9% versus -5.9% +/- 0.9%, p less than 0.05) in the involved segment. There was no increase in either subendocardial water content (78.6% +/- 0.1% versus 79.7% +/- 0.7%) or operative muscle stiffness (2.80 +/- 0.72 versus 2.36 +/- 0.42 mm Hg/mm) after the occlusion period. There were only mild to moderate ultrastructural alterations suggestive of reversible injury. In sharp contrast, reperfusion was associated with a 2.48% increase in subendocardial water content (p less than 0.05), a 42% increase in diastolic muscle stiffness (3.34 +/- 0.42 mm Hg/mm, p less than 0.05), and greater ultrastructural damage. We conclude that myocardial injury is significantly extended with unmodified blood reperfusion after temporary coronary occlusion.

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.

Effects of drugs and parenteral solutions on vascular fibrinolytic activity.

The effects of saline, D5W, D10W, dextran, penicillin, cephalothin, and the Renografin "dyes" on vascular fibrinolytic activity were evaluated in in vitro experiments and in caninne preparations. Saline, D5W, D10W, and dextran did not affect fibrinolytic activity. High concentrations of the Renografin "dyes" and penicillin decreased fibrinolytic activity in vitro. Cephalothin, with an increased association of postinfusion in vitro studies but demonstrated minimal effect during the in vivo studies during which sufficiently high local concentrations of drug may not have been obtained. It is concluded that, although intimal damage, stasis, and/or hypercoagulability are responsible for the development of post infusion thromboses, local hypofibrinolytic activity is induced by some infusions and might contribute to the persistence and propagation of the thromboses.

Right ventricular free wall ischemia: correlation of ischemic duration with extent of infarction in dogs.

The time dependence of myocardial necrosis has not been established for the right ventricle. In 16 dogs, we studied the temporal extension of ischemia-induced right ventricular free wall infarction for one hour (n = 8) and two hours (n = 8) followed by two hours of reperfusion, and quantitated segmental shortening, area at risk from ischemia, and area of necrosis. Stroke volume decreased 7.3 +/- 0.5 mL/beat (+/- standard error of the mean) in one hour (p less than 0.05) and 7.4 +/- 1.3 mL/beat in two hours (p less than 0.05). Segmental shortening was replaced by paradoxical motion in both groups during ischemia, and remained depressed throughout reperfusion. Right ventricular end-diastolic pressure increased with ischemia and then returned to normal during reperfusion. The extent of infarction appeared proportionate to the duration of ischemia, 13.2% +/- 4.1% at one hour and 66.9% +/- 4.5% at two hours (p less than 0.01). We conclude that the wave front of necrosis in the right ventricle progresses with duration of ischemia and that clinical techniques capable of limiting the duration of ischemia might salvage substantial amounts of right ventricular myocardium.

Heart rate-right ventricular stroke volume relation with myocardial revascularization.

Whether increasing pacing frequency in cardiac surgical patients effectively improves right ventricular cardiac index depends on the interrelationships between heart rate, stroke volume index, and end-diastolic volume index. If an inverse relation exists between heart rate and right ventricular volume then the decrease in right ventricular ejection fraction described after bypass may be due, in part, to changes in heart rate. We evaluated the effects of pacing at 80, 95, and 110 beats/min using a thermodilution volumetric catheter in 16 patients undergoing myocardial revascularization. End-diastolic volume index, stroke volume index, and stroke work index were significantly greater after bypass than before bypass, whereas right ventricular ejection fraction remained constant. Before and after bypass, sequentially increasing pacing frequency from 80 to 110 beats/min decreased stroke volume index by 28% to 35% (p less than 0.001), end-diastolic volume index by 12% to 14% (p less than 0.001), and right ventricular ejection fraction by 18% to 24% (p less than 0.001). Right ventricular performance, assessed by comparing the stroke volume index to end-diastolic volume index and stroke work index to end-diastolic volume index relations generated during pacing, was not altered by bypass. We conclude that sequentially increasing heart rate from 80 to 110 beats/min fails to improve stroke volume index and consequently cardiac index before or after cardiac operations. Intraoperatively, in patients with normal left ventricular function, increasing pacing frequency decreases right ventricular ejection fraction due to simultaneous reductions in stroke volume index and end-diastolic volume index.

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.

Efficacy of intravascular volume resuscitation in dogs with acute cardiac tamponade.

Whether cardiac tamponade causes myocardial ischemia and whether volume resuscitation can improve coronary perfusion pressure and myocardial blood flow were studied by hemodynamic responses to three blood infusions of 15 ml/kg in dogs with left ventricular hypovolemia produced by cardiac tamponade (N = 10) or hemorrhage (N = 10). Coronary perfusion pressure decreased to 37 +/- 2 mm Hg with tamponade and 39 +/- 1 mm Hg with hemorrhage, causing significant blood flow decreases in both ventricles. Myocardial oxygen extraction increased significantly in both groups without affecting lactate extraction. Volume resuscitation after hemorrhage progressively restored hemodynamic variables to baseline values. Volume resuscitation after tamponade did not increase stroke volume, whereas it increased coronary sinus pressure to 19.2 +/- 1.0 mm Hg (p less than 0.05). Coronary perfusion pressure increased to 53 +/- 5 mm Hg following the first infusion (p less than 0.05), but exhibited no further improvement. Tamponade did not produce myocardial ischemia. Coronary perfusion pressure and blood flow were not restored to baseline values with volume resuscitation since coronary sinus pressure rose incrementally with each volume infusion.

Technique of controlled reperfusion of the transplanted lung in humans.

BACKGROUND: Reperfusion injury remains a significant and sometimes fatal problem in clinical lung transplantation. Controlled reperfusion of the transplanted lung using white cell-filtered, nutrient-enriched blood has been shown recently to significantly ameliorate reperfusion damage in a porcine model. We modified this experimental technique and applied it to human lung transplantation. METHODS: Approximately 1,500 mL of arterial blood was slowly collected in a cardiotomy reservoir during the lung implant, and mixed to make a 4:1 solution of blood:modified Buckberg perfusate. This solution was passed through a leukocyte filter and into the transplant pulmonary artery for 10 minutes, at a controlled rate (200 mL/min) and pressure (less than 20 mm Hg), immediately before removal of the vascular clamp. RESULTS: Five patients underwent lung transplantation (1 bilateral, 4 single lung) using this technique. All patients were ventilated on a 40% fraction of inspired oxygen within a few hours and extubated on or before the first postoperative day. CONCLUSIONS: Controlled reperfusion of the transplanted lung with white cell-filtered, nutrient-enriched blood has given excellent functional results in our small initial clinical series.

Regional perfusion abnormalities with phenylephrine during normothermic bypass.

BACKGROUND: Hypotension and vasopressors during cardiopulmonary bypass may contribute to splanchnic ischemia. The effect of restoring aortic pressure on visceral organ, brain, and femoral muscle perfusion during cardiopulmonary bypass by increasing pump flow or infusing phenylephrine was examined. METHODS: Twelve anesthetized swine were stabilized on normothermic cardiopulmonary bypass. After baseline measurements, including regional blood flow (radioactive microspheres), aortic pressure was reduced to 40 mm Hg by decreasing the pump flow. Next, aortic pressure was restored to 65 mm Hg either by increasing the pump flow or by titrating phenylephrine. The animals had both interventions in random order. RESULTS: At 40 mm Hg aortic pressure, perfusion to all visceral organs and femoral muscle, but not to the brain, was significantly reduced. Increasing pump flow improved perfusion to the pancreas, colon, and kidneys. In contrast, infusing phenylephrine (2.4 +/- 0.6 micrograms.kg-1.min-1) increased aortic pressure but failed to improve splanchnic perfusion, so that significant perfusion differences existed between the pump flow and phenylephrine intervals. CONCLUSIONS: Increasing systemic pressure during cardiopulmonary bypass with phenylephrine causes significantly lower values of splanchnic blood flow than does increasing the pump flow. Administering vasoconstrictors during normothermic cardiopulmonary bypass may mask substantial hypoperfusion of splanchnic organs despite restoration of perfusion pressure.

Postischemic [Ca2+] repletion improves cardiac performance without altering oxygen demands.

The positive inotropism expected with correction of postischemic hypocalcemia might be counterbalanced by potential aggravation of reperfusion injury, in particular by calcium overload. We evaluated the effect of normalizing blood calcium concentration ([Ca2+]) on postischemic left ventricular systolic and diastolic mechanics using oxygen consumption and indices derived from pressure-diameter relations. In 10 open-chest dogs on cardiopulmonary bypass, the hearts underwent 30 minutes of normothermic global ischemia followed by one hour of multidose hypothermic (4 degrees C), hypocalcemic (0.3 mmol/L) blood cardioplegia. After reperfusion, systemic [Ca2+] had decreased to 70% of control (p = 0.017). The left ventricular inotropic state was significantly depressed from baseline (control) values, but was restored to baseline levels by resumption of normocalcemia after one hour of reperfusion. Chamber stiffness increased by 308% (p = 0.006) after hypocalcemic reperfusion but decreased significantly after [Ca2+] correction. Recovery of left ventricular performance with [Ca2+] correction did not augment myocardial oxygen consumption from the postischemic uncorrected state (5.0 +/- 0.3 mL O2/min/100 g versus 5.3 +/- 0.3 mL O2/min/100 g). We conclude that normalizing [Ca2+] after blood cardioplegia improves postischemic left ventricular performance without adversely affecting compliance or oxygen consumption.