Empty Beating Hearts Research Articles

Neonatal myocardial oxygen consumption during ventricular fibrillation, hypothermia, and potassium arrest

Many investigators have examined oxygen consumption in adult heats under conditions that simulate those encountered during cardiac operations and those that approximate basal metabolism. Few studies, however, have addressed this issue in neonatal myocardium. Hearts from 3- to 9-day-old piglets were studied in a blood-perfused isolated heart preparation in working, empty beating, fibrillating, potassium chloride-arrested (at 37 degree C and 15 degree C), and hypothermic (15 degree C) states. Oxygen consumption (expressed in milliliters of O2 per 100 g of ventricular tissue per minute; mean +/- standard deviation) was 6.69 +/- 1.91 for working hearts and fell to 3.19 +/- 1.08 for empty-beating hearts, 3.72 +/- 0.84 for fibrillating hearts, 1.30 +/- 0.34 for potassium-arrested hearts at 37 degree C, 0.37 +/- 0.18 for hypothermic (15 degree C) hearts, and 0.32 +/- 0.10 for potassium-arrested hearts at 15 degree C. All values were significantly different except the two obtained at 15 degree C. Vented fibrillating hearts used more oxygen than empty beating hearts. The addition of an arresting concentration of KCl did not lower oxygen consumption below that observed with hypothermia alone at 15 degree C. If potassium-based cardioplegia is incrementally beneficial in neonatal myocardial protection over that afforded by hypothermia alone, its effects cannot be explained by reduction in oxygen demand.

Myocardial protection for cardiac surgery.

The vast majority of cardiac surgical procedures are carried out using aortic cross-clamping and cardioplegie arrest [1]. Although alternate approaches such as operating on the normothermic empty beating heart, intermittent aortic cross-clamping or hypothermic ventricular fibrillation can be successfully utilized, the ability to carry out a meticulous and complete surgical procedure is generally best accomplished with the heart bloodless and still. Protective strategies in cardiac surgery are directed at both minimizing and reversing myocardial injury, which may occur not only secondary to ischemia induced with aortic cross-clamping, but also at the time of reperfusion. The ability to protect and resuscitate the heart from ischemic/reperfusion injury is of particular importance in patients with severe or complex disease, acute ischemia and/or compromised ventricular function.

Influence of temperature on the response time of mitochondrial oxygen consumption in isolated rabbit heart.

1. In this study we determined the temperature dependence of the mean response time of cardiac mitochondrial oxygen consumption following steps in metabolic demand. Metabolic demand was altered by stepwise changes in heart rate or in left ventricular volume at 20 and 28 degrees C. 2. Ten isolated rabbit hearts were perfused with Tyrode solution at constant oxygen tension and constant arterial flow. A balloon was inserted in the left ventricle and developed pressure was measured. Coronary venous oxygen tension was measured continuously with a Clark-type oxygen electrode. 3. The mean response time of mitochondrial oxygen consumption is defined as the first statistical moment of the impulse response function. This mean response time of mitochondrial oxygen consumption, following the change in metabolic demand, is calculated from the measured mean response time for the change in coronary venous oxygen tension by subtracting the transport time resulting from diffusion and convective transport in the blood vessels. The transport time is obtained from a model for oxygen transport developed previously. Experimental data, necessary for the model calculation, were obtained from measurement of the coronary venous oxygen tension transients following stepwise changes either in arterial oxygen tension or perfusion flow. 4. The calculated mean response times of mitochondrial oxygen consumption were 26.9 +/- 3.0 s (mean +/- S.E.M.) at 20 degrees C and 14.9 +/- 1.0 s at 28 degrees C. The mean response times of mitochondrial oxygen consumption did not differ significantly for steps in heart rate and in left ventricular volume and between upward and downward steps. 5. We suggest that intracellular calcium concentration is not the sole regulator of mitochondrial oxygen consumption in the isolated rabbit heart, since steps in heart rate and in left ventricular volume showed the same time course of oxygen uptake. 6. The mean response time of mitochondrial oxygen consumption obtained in the isolated rabbit heart at 20 degrees C did not differ significantly from the mean response time of mitochondrial oxygen consumption of isolated rabbit papillary muscle. After combining our data with previously published data on empty beating hearts at 37 degrees C, a Q10, which is the factor by which the mean response time of mitochondrial oxygen consumption increases per 10 degrees C decrease in temperature, of 2.1 was calculated.

Myocardial Blood Flow and Oxygen Consumption in the Empty-Beating, Fibrillating, and Potassium-Arrested Hypertrophied Canine Heart

Myocardial oxygen consumption and blood flow distribution were examined in severely hypertrophied canine hearts in the empty-beating, fibrillating, and pharmacologically arrested states. Hypertrophy was produced using a subcoronary valvular aortic stenosis model that mimics the clinical situation of aortic valvular stenosis. Oxygen content of the total coronary sinus collection was compared with a large volume arterial sample using a Lex-O 2-Con-TL analyzer, which had been validated by the Van Slyke-Neill method. Transmural blood flow was measured in each state using microspheres, and perfusion pressure was maintained at 80 mm Hg. Oxygen consumption in the empty-beating hypertrophied heart was found to be the same as that previously reported for normal hearts. Blood flow was evenly distributed in the empty-beating heart, with an endocardial/epicardial ratio of 0.99 ± 0.15 (SEM) milliliters per minute per gram of left ventricular weight. Oxygen consumption failed to increase significantly with fibrillation; however, blood flow distribution favored the subepicardium, suggesting that oxygen consumption determinations in the fibrillating hypertrophied heart may not accurately reflect metabolic demand. Basal oxygen consumption of the hypertrophied heart as determined by the potassium-arrested, blood-perfused model was the same as that previously described for normal hearts. Blood flow during potassium arrest favored the sub-endocardium (endocardial/epicardial ratio = 1.14 ± 0.27 ml/min/gm LV weight).

Myocardial flow distribution. II : Empty beating heart, ventricular fibrillation and cardiac arrest.

Myocardial oxygen consumption (MVO2) and coronary blood flow (CBF) distribution were studied in 21 isolated, metabolically supported dog hearts. Measurements of MVO2 and CBF distribution were carried out in three different experimental conditions : empty beating heart (EBH), ventricular fibrillation (VF) and high potassium-induced cardiac arrest (CA). MVO2 was approximately the same in EBH and VF (4.09 +/- 0.77 and 4.28 +/- 0.68 ml O2 min-1 100 g-1 respectively), and significantly lower in the group with CA (2.40 +/- 0.18 ml O2 min-1 100 g-1, P less than 0.05). Total CBF showed no significant differences among the three groups (84 +/- 7 ml/min in EBH; 78 +/- 7 ml/min in VF and 83 +/- 7 ml/min in CA). Subendocardial CBF per unit of tissue mass was significantly lower in hearts with VF (0.43 +/- 0.01 ml/min-1 g-1, P less than 0.05) when tested against the other two groups of experiments (0.69 +/- 0.03 ml min-1 g-1 in EBH and 0.65 +/- +/- 0.04 ml min-1 g-1 in CA). This was also reflected in the endo/epi ratio, that was significantly lower in VF (1.41 +/- 0.07, P less than 0.05) with respect to the other two groups (2 +/- 0.09 in EBH and 2.21 +/- 0.07 in CA). From data presented here we can conclude that cardioplegia, even in absence of hypothermia, is a method that will assure myocardial protection providing : (1) a lower subendocardial MVO2; (2) a higher subendocardial CBF, which helps for a prompt recovery during reperfusion.

Pressure-flow characteristics of the coronary collateral circulation during cardiopulmonary bypass. Effects of ventricualr fibrillation.

Even though ventricular fibrillation is used frequently during cardiopulmonary bypass (CPB), the effects of fibrillation on myocardial regions supplied by collateral vessels have not been determined. To study these effects, nine dogs with left ventricles (ameroid model) consisting of a region of myocardium supplied by collateral vessels (CR) and a region supplied by normal coronary arteries (NR) were subjected to normothermic CPB at two perfusion pressures. In both the empty beating heart (EBH) and empty fibrillating heart (EFH) regional myocardial flow was determined by tracer microspheres. Retrograde coronary pressure was measured via cannulation of the circumflex artery distal to the ameroid induced occlusion. When perfusion pressure was maintained at 80 mm Hg, retrograde coronary pressure was similar in the EBH (46 +/- 4 mm Hg) and in the EFH (48 +/- 3 mm Hg). During fibrillation subendocardial flow in the CR was unchanged, while flow in the NR increased (P less than 0.02). In addition, the endo/epi was greater in the NR than in the CR (P less than 0.01), a difference which did not exist in the EBH. The flow response to fibrillation in the CR could be produced in the NR by reducing the perfusion pressure to 50 mm Hg. These data suggest that during CPB, fibrillation exaggerates existing subendocardial perfusion deficits in collateral regions and the impaired flow response appears to be related to a low regional intravascular pressure.

Myocardial lipid metabolism in cardiac hyper- and hypo-function. Studies on triiodothyronine-treated and transplanted rat hearts.

Lipid composition of the myocardium and in vitro lipid metabolism were studied in hearts from young rats after 30 days of treatment with triiodothyronine (100 microgram/kg per day) and in heterotopically isotransplanted hearts of inbred adult rats 6 days after surgery. The former served as an experimental model of cardiac hyperfunction, while the latter, empty beating hearts, served as a model of cardiac hypofunction. In hearts from hyperthyroid animals the concentration of phosphatidylcholine, phosphatidylethanolamine, cardiolipin, and the incorporation of 14C-labelled palmitic and erucic acid into these phospholipids were increased significantly as compared with controls. In contrast, the triglyceride concentration and the incorporation of palmitate into triglyceride was significantly decreased. In transplanted hearts, the phospholipid concentration and the incorporation of 14C-labelled fatty acids into phospholipids were significantly decreased as compared with the hearts of the inbred host rats of the same age. The results indicate that the mechanical performance of the heart affects the phospholipid composition, which may be a reflection of increased or decreased proliferation of subcellular membranes in sustained cardiac hyper- or hypo-function.

Quantification of collateral resistance in acute and chronic experimental coronary occlusion in the dog.

The resistance to coronary blood flow in various parts of the myocardium was studied with the tracer microspheres technique before and immediately after an acute coronary occlusion and several weeks after a more slowly occurring coronary occlusion by Ameroid constrictor. All experiments were carried out in the isolated, metabolically supported, empty, beating dog heart at maximal coronary vasodilation induced with adenosine. Coronary resistance of the normal empty beating heart at maximal coronary vasodilation was 0.20 mm mm Hg/(ml/min) per 100 g of tissue (subepicardium) and 0.16 mm Hg/(ml/min) per 100 g of tissue (subendocardium). After acute coronary occlusion the perfusion of the subtended myocardium was maintained at a much lower level by way of collateral vessels, which showed a resistance to flow of 3.52 mm Hg/(ml/min) per 100 g. If coronary artery occlusion proceeded more slowly the collateral vessels became more functional and myocardial infarction was avoided. During collateral enlargement collateral resistance fell from 3.52 to 0.22 mm Hg/(ml/min) per 100 g within a period of 8 weeks after implantation of the constricting device. The degree of compensation by collaterals for the loss of the occluded native coronary artery was 33% of its former conductance.

EFFECTS OF ACETYLSTROPHANTHIDIN ON CORONARY VASCULAR RESISTANCE AND MYOCARDIAL OXYGEN CONSUMPTION.

The effects of acetylstrophanthidin on coronary circulation were studied in 31 dogs. Coronary blood flow was measured in empty beating hearts or in fibrillating hearts by collecting coronary venous return during perfusion of the systemic circulation (cardiopul-monary bypass). In 14 animals with ventricular fibrillation, acetylstrophanthidin caused an initial coronary constriction and fall in coronary blood flow. This was followed, after approximately 10 minutes, by a significant drop in resistance and a rise in coronary blood flow which persisted for the remainder of the experiment. Associated with the increase of blood flow was an increase of myocardial oxygen consumption. This effect was not abolished by ganglionic blockade, cardiac denervation or bilateral adrenalectomy. In nine dogs with beating but empty hearts, after the initial constriction of the coronary vessels, there was only a small change in coronary blood flow and resistance, although myocardial oxygen consumption was increased. The lack of coronary vasodilatation was attributed to increased mechanical resistance due to the augmented force of contraction produced by the drug.

Oxygen uptake of the nonworking left ventricle.

Comparisons have been made in the open chest dog of the oxygen usage of the left ventricle whose external work has been reduced to zero by 4 different procedures. The average oxygen usage of the left myocardium/100 Gm./min. is about 2.0 cc. in complete arrest with vagal stimulation or with intracoronary potassium injection; 3.8 cc. in fibrillation; and 3.4 cc. in the empty but beating heart. The oxygen value in the arrested heart approximates 27 per cent of that in the control state and the uptake during vagal stoppage varies directly with the control metabolic level. In the fibrillating ventricle the higher values are related to the intensity of fibrillatory movements, and in the empty beating heart to the control metabolic rate and to the frequency of the heart beat. The experiments with vagal arrest also permit estimation of the oxygen debt of the myocardium.