Effects of systemic hypothermia on myocardial metabolism and coronary blood flow in the fibrillating heart.

Ventricular fibrillation during normothermic cardiopulmonary bypass is deleterious to the myocardium. This study was undertaken to determine if moderate systemic hypothermia would protect the myocardium during ventricular fibrillation. Fourteen mongrel dogs were subjected to 1 hour, 15 minutes of total cardiopulmonary bypass. Ventricular fibrillation was induced by a continuous electrical alternating current applied at the beginning of bypass and lasting for 1 hour. Six animals were maintained at normothermia (Group I), and eight were cooled to 30 degrees C. for 1 hour (Group II). The hypothermic group (Group II) demonstrated lower myocardial oxygen consumption and metabolism, decreased coronary blood flow, and less myocardial lactate production during ventricular fibrillation than did Group I. It is concluded that hypothermia does offer some protection, although not complete, against the deleterious effects of ventricular fibrillation described previously.     

Effects of adenosine on myocardial blood flow and metabolism after coronary artery bypass surgery

The effects of adenosine on myocardial blood flow and metabolism, central hemodynamics, and the intrapulmonary shunt fraction were investigated. Fourteen patients with two- or three-vessel coronary artery disease and with an ejection fraction greater than 0.5 were studied in the operating room following sternal closure after elective coronary artery bypass grafting. Systemic and pulmonary hemodynamics and global (coronary sinus), as well as regional myocardial blood flow (great cardiac vein flow), and metabolic variables were measured. Adenosine was given in infusion rates of 15, 30, 60, and 120 micrograms.kg-1.min-1. Infusion rates of 60 and 120 micrograms.kg-1.min-1 decreased mean arterial blood pressure (11% and 16%, respectively), systemic vascular resistance index (30% and 43%), and pulmonary vascular resistance index (24% and 31%), increased cardiac index (25% and 45%), heart rate (14% and 15%), and stroke volume index (9% and 25%), and had no effect on central filling pressures. These infusion rates doubled the intrapulmonary shunt fraction and decreased arterial O2 tension by 26%. Great cardiac vein flow and coronary sinus flow increased 60% with adenosine infusion of 30-60 micrograms.kg-1.min-1 and 120% with 120 micrograms.kg-1.min-1. The ratio of great cardiac vein flow to coronary sinus flow, regional myocardial oxygen consumption, and mean regional lactate extraction and uptake were not significantly altered by adenosine. Adenosine caused a significant depression of the ST segment at infusion rates of 60 and 120 micrograms.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of tracheal extubation on coronary blood flow,myocardial metabolism and systemic haemodynamic responses

Global coronary blood flow and metabolism were measured in seven patients on the first postoperative day following coronary revascularization to test the hypothesis that tracheal extubation produces adverse haemodynamic responses akin to those observed during tracheal intubation. Regional coronary flow and metabolic measurements were made in five of the seven patients. Extubation from a continuous positive airway pressure (CPAP) of 5 cm H₂O was associated with a statistically significant rise in cardiac index from 3.44 ± 0.23 L · min^-1 · m^-2 to 3.73 ± 0.15L·min^-1 ·m^-2 related to an increase in stroke index, without significant changes in heart rate, mean arterial and pulmonary capillary wedge pressure. Consequently the changes in myocardial oxygen consumption (8.52 ± 0.55 to 8.85 ± 0.93 ml · min^-1) and coronary blood flow (172 ± 18 to 179 ± 17 ml·min^-1) were less prominent than those reported during intubation, where substantial rises in myocardial oxygen consumption and coronary flow occurred. Two patients experienced cardiac lactate production but there were no changes in systemic or coronary haemodynamics, nor were there clinical or electrocardiographic signs of ischaemia. We conclude that extubation does not appear to be associated with adverse systemic or coronary haemodynamic responses in patients following coronary bypass grafting. However, the revascularized myocardium may remain vulnerable to anaerobic metabolism in the immediate postoperative period. Pour savoir si comme ľintubation, ľextubation de la trachée provoque des perturbations hémodynamiques, on a mesuré le métabolisme et la circulation coronarienne globale chez sept patients, au lendemain ďun pontage aorto-coronarien. On a aussi calculé les valeurs régionales de ces mêmes variables pour cinq ďentre eux. Ľindex cardiaque de 3.44 ± 0.23 L · min^-1 · m^-2 sous pression positive en respiration spontanée (CPAP) de 5 cm. H₂O s’est élevé à 3.73 ± 0.15 L · min^-1 · m^-2 post-extubation avec une augmentation significative du volume ďéjection. La fréquence cardiaque et les pressions artérielles moyennes et capillaires pulmonaires n’ont pas changé. Ainsi ľaugmentation de la consommation ďoxygène du myocarde de 8.52 ± 0.55 à 8.85 ± 0.93 ml · min^-1 et celle du flot coronarien de 172 ± 18 à 179 ± 17 ml · min^-1 ont été moindres que celles, importantes, déjà observées lors de ľintubation. On a noté chez deux patients une production de lactate par le myocarde, sans changement de ľhémodynamic systémique et coronarienne non plus que de signe clinique ou électrocardiographique ďischémie. Donc, après un pontage coronarien, ľextubation ne semble pas causer ďeffet néfaste sur les circulations systémique et coronarienne, toutefois, le myocarde revascularisé peut demeurer sensible au métabolisme anaérobique.     

Effects of intubation on coronary blood flow and myocardial oxygenation

Effects on haemodynamics and myocardial oxygenation of endotracheal intubation were examined in 17 patients after halothane induction and 12 after 1 mg X kg-1 of IV morphine. Six patients having each anaesthetic were pretreated with IV propranolol (0.1 mg X kg-1) 45 minutes earlier. Arterial and intracardiac pressures, cardiac output and total coronary sinus blood flow (CSBF), both by thermodilution, were determined plus arterial-coronary differences of oxygen, haemoglobin and lactate. Blood pressure (BP), heart rate and CSBF were recorded continuously during intubation. The subjects were candidates for coronary bypass grafts, but had good ventricular function (mean ejection fraction 0.68 +/- 0.13 SD). From their reduced levels after induction, BP, cardiac index and systemic vascular resistance increased to awake levels following intubation. Mean CSBF in nonbetablocked patients increased to awake level along with BP. More myocardial oxygen was extracted and consumed after intubation, but lactate extraction continued: these data are evidence of adequate oxygen supply. Induction with either halothane or morphine effectively prevented the hypertensive response to intubation. Acute beta blockade led to less increase in heart rate from intubation.     

Genuine effects of ventricular fibrillation upon myocardial blood flow, metabolism and catecholamines in patients with aortic stenosis

OBJECTIVE: Ventricular fibrillation (VF) is life-threatening because of its haemodynamic and metabolic effects. The purpose was to examine if VF also has primary effects per se. We therefore investigated the early effects of VF on myocardial blood flow, metabolic characteristics and catecholamine concentrations in patients undergoing surgery for aortic stenosis. DESIGN: The immediate effects of up to 5 min of VF were studied in 21 patients during cardiopulmonary bypass (CPB) before valve replacement. RESULTS: During VF the global myocardial oxygen consumption, coronary blood flow and vascular resistance were unchanged, and the mean arterial pressure (on CPB) decreased from 70 to 51 mmHg (p < 0.02). Fibrillation induced a high myocardial tone and a probable functional aortic insufficiency, which instantly equilibrated left ventricular and aortic pressures. Signs of myocardial ischaemia and acidosis developed after 4 min: a decrease in the pH of coronary sinus blood from 7.38 to 7.32 (p < 0.001), an increased release of lactate from 32 to 137 micromol/min (p < 0.001) and potassium from 29 to 73 micromol/min (p < 0.05). The noradrenaline net release increased from 0.021 to 0.58 nmol/min (p < 0.02) after 1.5 min of VF and then decreased. The adrenaline net uptake remained low and unchanged (17-28%). CONCLUSION: VF in patients with aortic stenosis was rapidly followed by myocardial ischaemia, acidosis and a transient increase in the myocardial noradrenaline net release despite sufficient coronary perfusion and unchanged global myocardial oxygen consumption. The VF instantly induced equilibration of left ventricular and aortic pressure and probably caused a relative underperfusion of the subendocardium. These factors all support persistence of VF.     

Effects of local cardiac hypothermia on the magnitude and distribution of coronary blood flow and on myocardial function and metabolism.

Changes in hemodynamics, metabolism, and the distribution and magnitude of coronary blood flow were evaluated in 10 dog hearts before and after 60 minutes of cardiac anoxia with the myocardium protected by local cardiac hypothermia. The data indicate that following myocardial protection with this technique, hemodynamic performance is not impaired very greatly and there is a noticeable reactive hyperemia, particularly to the subendocardial layers of the myocardium.     

Isoflurane: coronary blood flow and myocardial metabolism in patients with coronary heart disease

The effects of isoflurane on myocardial oxygen uptake, metabolism and coronary blood flow (argon washin-technique) were studied in 10 patients undergoing three-vessel coronary artery bypass surgery. All patients were men with stable angina and normal left ventricular function and were receiving maintenance doses of beta-receptor antagonists or calcium channel blocking drugs. Anaesthesia consisted of isoflurane and 50% nitrous oxide in oxygen. Measurements were performed and blood samples were taken with the patients awake, 20 min after induction of anaesthesia without surgical stimulation, and during sternotomy and sternal spread. End-tidal isoflurane concentrations averaged 0.4% after induction of anaesthesia and 1.5% during sternotomy. Isoflurane significantly decreased myocardial blood flow by 18% following induction of anaesthesia, while sternotomy increased myocardial blood flow to pre-induction levels. Induction decreased myocardial oxygen uptake by 32%, while sternotomy increased oxygen uptake by 21% vs post-induction values. Myocardial uptake of glucose, lactate, free fatty acids and pyruvate significantly decreased after induction and increased to pre-induction levels during sternotomy. Myocardial lactate production, indicating myocardial ischaemia, was observed in 1 patient after induction and in three patients during sternotomy; three additional patients demonstrated a marked reduction in myocardial lactate uptake after induction and during sternotomy. It is concluded that all changes in myocardial metabolism, oxygen uptake and coronary blood flow were the result of a decrease in haemodynamic load on the myocardium and reduced contractility, while the increase in these parameters during sternotomy was due to an increase in myocardial work.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral blood flow velocity during repeatedly induced ventricular fibrillation.

STUDY OBJECTIVE: To investigate the effect of induced ventricular fibrillation and defibrillation on cerebral blood flow (CBF) was investigated using a transcranial Doppler. DESIGN: Prospective clinical study. SETTING: University hospital. PATIENTS: 12 ASA physical status III and IV patients who underwent implantable cardioverter defibrillator placement during general anesthesia. INTERVENTIONS: Cerebral blood flow velocity was measured repeatedly during induced ventricular fibrillation and subsequent defibrillation. MEASUREMENTS AND MAIN RESULTS: The mean flow velocity in the middle cerebral artery was measured using a transcranial Doppler. The mean flow velocities decreased significantly immediately after ventricular fibrillation was induced, but they returned to preventricular fibrillation levels immediately after successful defibrillation. Repeatedly induced ventricular fibrillations have no cumulative detrimental effect on the CBF velocity. CONCLUSIONS: Repetitively induced ventricular fibrillation and defibrillation during the insertion of implantable cardioverter defibrillator did not show any detrimental changes in CBF. Transcranial Doppler may be a more sensitive device than other currently available cerebral monitors to detect changes in cerebral circulation during a brief episode of ventricular fibrillation and defibrillation.     

Cardiac output,coronary flow,ventricular fibrillation and survival following varying degrees of myocardial contusion

Varying degrees of myocardial contusion was produced in 10 dogs. Two animals died of left ventricular rupture. Six of the other eight developed ventricular fibrillation. Depression of cardiac output was significantly correlated with percentage myocardial contusion. None of the hemodynamic effects of contusion could be attributed to alterations in coronary flow to contused or non-contused portions of the heart. Attempts to quantitate degree of myocardial contusion may be useful in patients with blunt chest trauma.     

Effects of atrial fibrillation on coronary artery bypass graft flow.

OBJECTIVES: No detailed studies exist of coronary artery bypass graft flow during atrial fibrillation. We examined the effects on bypass graft flow of atrial fibrillation following coronary artery bypass grafting. METHODS: Immediately after surgical revisualization, atrial fibrillation was induced in 18 patients by high frequency atrial pacing. Hemodynamic variables were measured in sinus rhythm and atrial fibrillation. The graft flow in pedicled left internal thoracic artery grafts and in saphenous vein grafts was also measured using transit-time flowmetry. RESULTS: Left internal thoracic artery graft flow had a greater diastolic component than saphenous vein graft flow, as shown by the percent diastolic time-flow integral (86 +/- 10% in the left thoracic artery and 62 +/- 12% in the saphenous vein, P < 0.0001). The induced atrial fibrillation caused significant deterioration in hemodynamics: heart rate and central venous pressure increased, and mean arterial pressure and cardiac index decreased (all P < 0.0025). In left internal thoracic artery grafts (n = 18) and also in saphenous vein grafts (n = 20), graft flow decreased significantly with atrial fibrillation (44.3 +/- 26.2 to 26.2 +/- 20.7 ml/min in the left internal thoracic artery, P = 0.0003; 39.7 +/- 15.6 to 33.3 +/- 14.3 ml/min in the saphenous vein, P = 0.001). The reduction in graft flow due to atrial fibrillation was much larger in left internal thoracic artery grafts than in saphenous vein grafts (P = 0.0008). CONCLUSIONS: Direct measurement of coronary artery bypass graft flow shows that atrial fibrillation after surgery significantly reduces graft flow. The effect is much larger in left internal thoracic artery grafts with their strong diastolic component than in saphenous vein grafts.     

Total coronary blood flow measurements and myocardial metabolism during cardiopulmonary bypass in a canine model.

Myocardial respiratory function and total coronary blood flow were evaluated during cardiopulmonary bypass in 18 dogs. The fibrillating heart was found to be associated with an increase in myocardial oxygen utilization and metabolic rate which was compensated for by a corresponding increase in total coronary blood flow. Following anoxic arrest of the heart, there appears to be an initial impairment to oxygen utilization. Oxygen consumption does not return to normal after 15 minutes of restoring coronary blood flow. The stability of the experimental model as outlined in this study is thought to be related to the use of autologous blood in priming the extracorporeal circuit.     

Combined effects of verapamil and isoflurane on coronary blood flow and myocardial metabolism in the dog

The effects of three different plasma levels of verapamil on coronary hemodynamics and myocardial metabolism in the presence of 1.61 +/- 0.05% end-tidal concentration of isoflurane (mean +/- SEM) were studied in a canine model, using a thermodilution coronary sinus catheter to measure coronary sinus blood flow and pressure and to provide coronary sinus plasma samples. A control group receiving only isoflurane was also studied (n = 6). Plasma arterial verapamil levels of 55 +/- 7 (n = 6); 134 +/- 7 (n = 10); and 301 +/- 37 ng X ml-1 (n = 5), were achieved by a loading dose followed by a continuous infusion for 30 min. The only changes with time in the isoflurane group were decreases in left ventricular maximum rate of tension development (dP/dt) and left ventricular stroke work index compared with control after 90 min without changes in myocardial oxygen balance. The low plasma verapamil level caused reductions in heart rate, mean and diastolic arterial pressure, and left ventricular dP/dt without changes in myocardial oxygen supply or myocardial metabolism. Intermediate verapamil concentrations produced a transient initial increase in heart rate and a reduction in stroke volume index. With the intermediate and the highest levels of verapamil, mean and diastolic arterial pressure, left ventricular dP/dt, and cardiac index were decreased. An increase in arterial norepinephrine plasma levels was seen in the intermediate and the highest levels of verapamil; however, a transient coronary vasodilation occurred without changes in myocardial oxygen balance. Significant prolongation of the PR interval was observed in all verapamil groups, with second or third degree heart block in some of the higher-dose animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Restoration of myocardial bioenergetic metabolism in swine after periods of ischemic ventricular fibrillation.

Myocardial mitochondrial function and high energy phosphate levels were measured in normal swine, in swine after either 5 or 10 minutes of ischemic ventricular fibrillation (IVF) while on cardiopulmonary bypass, and in swine defibrillated after either 5 or 10 minutes of IVE. The damage to myocardial mitochondria induced by IVF, such as partial uncoupling, decreased oxygen uptake, and loss of cytochrome oxidase activity, was completely reversed almost instantly by coronary artery perfusion and the restoration of sinus rhythm. After either 5 or 10 minutes of IVF followed by coronary artery reperfusion and defibrillation, myocardial creatine phosphate (CP), adenosine monophosphate (AMP) and adenosine diphosphate (ADP) return to normal levels very rapidly. However, adenosine triphosphate (ATP) levels remain significantly lower than control levels. If the bioenergetic mechanisms of swine and human myocardium are similar, it appears that IVF at least for a 10 minute period produces no damage to myocardial mitochondria that is not corrected by perfusion of the coronary arteries and re-establishment of sinus rhythm. Furthermore, sinus rhythm can be re-established and maintained despite signficantly lower levels of myocardial ATP.     

Regional myocardial blood flow and coronary vascular reserve in unanesthetized ponies during pacing-induced ventricular tachycardia

To examine the effects of tachycardia on coronary circulation, transmural distribution of myocardial blood flow (MBF, 15-μm diameter radionuclide-labeled microspheres) was studied in six healthy adult ponies at rest (heart rate = 60 ± 7 beats · min^?1), during ventricular pacing at 150 and 200 beats · min^?1, as well as with ventricular pacing at 250 beats · min^?1 before and during maximal coronary vasodilatation (iv adenosine infusion; 4 μmole · kg^?1 · min^?1). Mean aortic pressure and cardiac output were unchanged from control values with ventricular pacing. Whereas ventricular pacing at 150 and 200 beats · min^?1 resulted in a progressive uniform increase in transmural MBF and well-maintained endo:epi perfusion ratio, pacing at 250 beats · min^?1 did not result in a further increase in MBF compared to pacing at 200 beats · min^?1 and the left ventricular (LV) subendocardial:subepicardial (endo:epi) perfusion ratio was significantly less than 1.00 (0.87 ± 0.05). Blood flow to the LV papillary muscles and subendocardium was significantly less than that recorded at 200 beats · min^?1. The LV endo:epi perfusion ratio with ventricular pacing at 250 beats · min^?1 during adenosine infusion resulted in a decrease in mean aortic pressure (63% of control value) and a marked further reduction in blood flow to the LV papillary muscles as well as the LV subendocardium, while MBF increased dramatically in the LV subepicardium compared to values observed during ventricular pacing at 250 beats · min^?1 alone. This resulted in a LV endo:epi perfusion ratio of 0.39 ± 0.09. By contrast, transmural right ventricular (RV) MBF increased significantly and the RV endo:epi perfusion ratio was well maintained. These data demonstrate that coronary vasomotion functions to maintain LV subendocardial blood flow in the pony myocardium at a heart rate of 200 beats · min^?1, while at 250 beats · min^?1 exhaustion of coronary vasodilator reserve in the deeper layers limits further increase in MBF.     

Esmolol decreases the adverse effects of acute coronary artery occlusion on myocardial metabolism and regional myocardial blood flow in dogs

This study was designed to test the hypothesis that beta-adrenergic receptor blockade with esmolol would decrease the hemodynamic and myocardial metabolic impairment produced by left anterior descending coronary artery (LADa) occlusion. Twenty-three anesthetized open-chest dogs underwent direct cannulation of the LADa, its companion vein (LADv), and a distal circumflex vein (CFXv) for blood sampling. All dogs were subjected to two consecutive 15-minute periods of total LADa occlusion; group 1 (n = 11) received an infusion of esmolol (150 micrograms.kg-1.min-1) during either occlusion period (randomly assigned) and group 2 (n = 12) received no intervention during either occlusion period. One hour of reperfusion was interposed between the two periods of LADa occlusion. Hemodynamic measurements were made and blood was sampled from the aorta, CFXv, LADa, and LADv before and during both periods of LADa occlusion. Without esmolol infusion, LADa occlusion was associated with decreases in stroke index, coronary perfusion pressure, and left ventricular stroke work index; with esmolol infusion these hemodynamic decrements did not occur. During both LADa occlusion periods in both groups, lactate extraction became negative, i.e., there was net lactate production. Despite this, the magnitude of lactate production was less with esmolol than without it. Finally, average endocardial-to-epicardial blood flow ratio in the LAD perfusion area was decreased during each LAD occlusion period except when esmolol was infused, during which the baseline value was maintained. Thus, infusion of esmolol during temporary LADa occlusion preserved certain hemodynamic variables, preserved the ratio of endocardial-to-epicardial blood flow, and decreased the apparent magnitude of lactate production.