Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic mice

Altered cardiac metabolism and function (diabetic cardiomyopathy) has been observed in diabetes. We hypothesize that cardiac efficiency, the ratio of cardiac work (pressure-volume area [PVA]) and myocardial oxygen consumption (MVo(2)), is reduced in diabetic hearts. Experiments used ex vivo working hearts from control db/+, db/db (type 2 diabetes), and db/+ mice given streptozotocin (STZ; type 1 diabetes). PVA and ventricular function were assessed with a 1.4-F pressure-volume catheter at low (0.3 mmol/l) and high (1.4 mmol/l) fatty acid concentrations with simultaneous measurements of MVo(2). Substrate oxidation and mitochondrial respiration were measured in separate experiments. Diabetic hearts showed decreased cardiac efficiency, revealed as an 86 and 57% increase in unloaded MVo(2) in db/db and STZ-administered hearts, respectively. The slope of the PVA-MVo(2) regression line was increased for db/db hearts after elevation of fatty acids, suggesting that contractile inefficiency could also contribute to the overall reduction in cardiac efficiency. The end-diastolic and end-systolic pressure-volume relationships in db/db hearts were shifted to the left with elevated end-diastolic pressure, suggesting left ventricular remodeling and/or myocardial stiffness. Thus, by means of pressure-volume technology, we have for the first time documented decreased cardiac efficiency in diabetic hearts caused by oxygen waste for noncontractile purposes.     

Monitoring weaning from BIVAD Thoratec with peak oxygen consumption

A biventricular assistance device has been implanted in a young woman for a peripartum cardiac failure. An intended weaning consisted of gradual reloading and exercise training monitored with peak oxygen consumption (VO(2)) and radionuclide-left ventricle ejection fraction. Progressive increase in peak VO(2) during partial assistance occurred more than 2 months, from 10.3 to 19 mL.kg(-1).min(-1). Successful explantation was realized when peak VO(2) exceeded 15 mL.kg(-1).min(-1) and radionuclide-left ventricle ejection fraction was more than 40% during off-pump testing.     

Direct compression of the failing heart reestablishes maximal mechanical efficiency

BACKGROUND: In failing hearts, homeostatic mechanisms contrive to maximize stroke work and maintain normal arterial blood pressure at the expense of energetic efficiency. In contrast dobutamine reestablishes maximal mechanical efficiency by promoting energetically optimal loading conditions. However, dobutamine also wastefully increases nonmechanical oxygen consumption. We investigated whether direct mechanical cardiac compression would reestablish maximal mechanical efficiency without the oxygen-wasting effect. METHODS: The pressure-volume relationship and myocardial oxygen consumption were derived in sheep using left ventricular pressure and volume from manometer-tipped and conductance catheters, and coronary flow from Transonics flow probe. RESULTS: Propranolol hydrochloride and atropine sulfate were administered to reduce ejection fraction to 21% when ventricular elastance fell to 1.35 mm Hg/mL and mechanical efficiency to 79% of maximal. Low-pressure direct mechanical compression of the failing heart restored mechanical efficiency to 94% of maximal and realigned optimal left ventricular end-systolic pressure with operating left ventricular end-systolic pressure without altering nonmechanical oxygen consumption. CONCLUSIONS: We conclude that direct cardiac compression restores mechanical efficiency to normal maximum without wasting energy on additional nonmechanical activity.     

Nitrous oxide added to halothane reduces coronary flow and myocardial oxygen consumption in patients with coronary disease

The haemodynamic and myocardial metabolic effects of adding 50 per cent nitrous oxide to 0.5 per cent halothane were studied in 13 patients, before the surgical incision for coronary artery vein grafts. Cardiac output and coronary sinus blood flow were determined by thermodilution, along with haemodynamic measurements. Measurements 15 minutes after addition of nitrous oxide revealed a significant decrease in heart rate, arterial pressure, cardiac index, coronary sinus blood flow and myocardial oxygen consumption. There was a significant increase in coronary sinus lactate content, and a significant decrease, from 27 to 11 per cent, in myocardial lactate extraction. We conclude that these circulatory changes were likely to be due to a depression of ventricular function by the nitrous oxide. The myocardia of these patients with severe coronary disease were becoming globally ischaemic while they were receiving 50 per cent oxygen, in the presence of hypotension. Nitrous oxide should be turned off when hypotension occurs in coronary patients.     

New aspects of myocardial oxygen consumption. Invited review

This paper gives an overview of mainly new aspects of myocardial oxygen consumption. Experimental models have quantified energy consumption in mechanical work, excitation-contraction coupling and metabolic processes. However, there are still contradictory observations between hemodynamic, thermodynamic and subcellular models and further knowledge of subcellular energy consumption is anticipated. The energy cost of contractility-enhancing drugs has been investigated in various experimental and clinical studies, and the calcium sensitizers have been proven to be the most mechanoenergetically efficient. An "oxygen-wasting" effect in post-ischemic hearts was observed some 15 years ago. The mechanism for this inefficiency has been thoroughly investigated, and seems to be caused by an inefficient excitation-contraction coupling and/or inefficiency in the contractile apparatus. The mechanoenergetic efficiency in heart failure needs further investigation.     

Preoperative metoprolol improves cardiovascular stability and reduces oxygen consumption after thoracotomy

Background : Increased sympathetic activity perioperatively and associated cardiovascular effects play a central role in cardiovascular complications. High thoracic epidural blockade attenuates the sympathetic response, but even with complete pain relief, haemodynamic and endocrine responses are still present. Beta–adrenoceptor blockade is effective in situations with increased sympathetic activity. This study was designed to evaluate the perioperative haemodynamic effect of preoperative βblockade and its influence on the haemodynamic aspects of the surgical stress response.
Methods : Thirty–six otherwise healthy patients undergoing elective thoracotomy for lung resection were randomised doubleblinded to receive either 100 mg metoprolol or placebo preoperatively. Anaesthesia was combined high thoracic epidural block and general anaesthesia. The epidural analgesia was continued during recovery. Patients were monitored with ECG, pulse oximetry, invasive haemodynamic monitoring, arterial blood gases and electrolytes.
Results : After induction of anaesthesia the mean arterial pressure (MAP) decreased in both groups, and decreased further in the placebo group after initiation of the epidural block. The heart rate (HR) was slightly less throughout the observation period after metoprolol. Peroperatively, the only difference in measured haemodynamics was a marginally higher MAP after metoprolol. Postoperative cardiac index (CI) was lower with a lower variability and cardiac filling pressures were slightly higher in the metoprolol group. The oxygen consumption index was higher after placebo throughout the observation period, with no difference in the oxygen delivery.
Conclusion. We found that preoperative β–blockade during combined general anaesthesia and high thoracic epidural blockade stabilised perioperative HR and CI and decreased total oxygen consumption.     

The Impella Recover microaxial left ventricular assist device reduces mortality for postcardiotomy failure: a three-center experience

BACKGROUND: We evaluated patient outcomes and complications associated with the microaxial Impella Recover left ventricular assist device (Impella Cardiosystems AG, Aachen, Germany) for postcardiotomy low-output syndrome. This low-cost device is inserted across the aortic valve through a 10-mm vascular graft sewn to the ascending aorta. METHODS: Impella patients were compared with 198 patients treated with an intraoperative intra-aortic balloon pump between January 2000 and December 2002. Three risk scores were used: the Hausmann score, the Texas Heart Institute score, and the Cleveland intensive care unit score. Between September 2001 and March 2003, 24 patients were treated with the Impella Recover for low-output syndrome. Before device insertion, 21 could not be separated from cardiopulmonary bypass, and 3 had postoperative hemodynamic instability despite high-dose catecholamines. Sixteen were treated with the Impella and intra-aortic balloon pump and 8 with the Impella alone (no intra-aortic balloon pump because of peripheral vascular disease or because deemed unnecessary). RESULTS: No technical problems with device insertion occurred. Pump flow was 3.3 +/- 0.7 L/min at 28,000 +/- 4500 RPM. Support time was 61 +/- 56 hours (range, 7-228 hours). Four devices required repositioning. One device failed (leaking purge line) and was removed. Hemolysis was minimal (lactate dehydrogenase levels of 540 +/- 260 U/dL for Impella survivors). Mortality for Impella patients was 54% (13/24), similar to that for high-risk intra-aortic balloon pump patients (Hausmann score > or =2 [57%], intensive care unit score > or =2 [51%], Texas Heart Institute score > or =0.75 [55%], and cardiac index < or =2.3 [45%]). Cardiac output data were available in 19 Impella patients. Impella patients able to increase their cardiac output to 1 L/min or more above the pump flow of the Impella Recover had a 10% (1/10) mortality, versus 88% (8/9) in patients with a residual cardiac function of 1 L/min or less (P =.001). Comparison of high-risk intra-aortic balloon pump patients with Impella patients with residual cardiac function of 1 L/min or more showed a significant reduction in mortality, regardless of the high-risk definition used. Residual cardiac function was the strongest predictor of survival in Impella patients. CONCLUSIONS: The Impella Recover device provides 3 to 4 L/min flow. It improves survival in patients with low-output syndrome if the heart is able to pump 1 L/min or more above device flow.     

Coronary sinus blood flow and myocardial oxygen consumption after valve replacement for aortic insufficiency

Seven cases are reviewed in which the aortic valve was replaced with a Bj?rk-Shiley tilting disk valve to treat aortic insufficiency. Comparative studies were made to determine coronary sinus blood flow (CSF) and myocardial oxygen consumption (MVO2) by using a continuous thermodilution method both before and after the operation. Additionally, indexes of left ventricular function were obtained by catheterization of the right and left heart and by left ventriculography. Postoperative total CSF decreased significantly compared with the preoperative value (p less than 0.02). However, in all cases, the postoperative CSF per 100 g of left ventricle (LV) increased compared with the preoperative measurement (p less than 0.001). The CSF per beat per 100 g LV also increased postoperatively (p less than 0.001). Total MVO2 decreased postoperatively (p less than 0.02). However, the MVO2 per unit mass tended to increase postoperatively; these increases were not significant. Postoperatively the left ventricular mass and left ventricular wall stress decreased considerably. The left ventricular ejection fraction (EF) and the mean velocity of circumferential fiber shortening (mVCF) remained at normal levels, whereas the left ventricular function improved markedly. In short, the total CSF decreased, along with LVM and left ventricular wall stress. However, because CSF per unit mass increased and EF and mVCF remained at normal values, it is assumed that the increase in CSF is associated with improvement in postoperative contractility.     

Hemodynamic parameters in the evaluation of myocardial oxygen consumption during anesthesia

Direct measurements of myocardial oxygen consumption (MVO2) and of a number of hemodynamic variables were performed in 60 patients with coronary heart disease undergoing three-vessel coronary artery bypass surgery. Anesthetic procedures included halothane, enflurane, isoflurane, propofol fentanyl, midazolam/fentanyl, and morphine anesthesia. The following hemodynamic variables were correlated with MVO2: systolic pressure (Psyst), mean arterial pressure (Part), heart rate (HR), cardiac index (CI), stroke volume index (SVI) and arithmetic combined variables: Psyst x square root (HR), Part x square root (HR), Psyst x HR, Part x HR, Psyst x HR x ta(ejection time), Part x HR x ta, Psyst x CI, Part x CI. The product of Psyst x square root (HR) is equivalent to the tension/time index as modified by Bretschneider and the product Psyst x HR x ta is equivalent to the tension/time index of Sarnoff as modified by Robinson. Production and uptake of lactate as metabolic equivalents of myocardial oxygenation were also correlated with myocardial oxygen consumption. Measurements were performed with the patients awake, after induction of anesthesia without surgical stimulation, during sternotomy and after the operation. We obtained 209 evaluable measurements (MVO2 vs hemodynamic variables). The single hemodynamic variables that correlated best with MVO2 was systolic pressure (r = 0.67). Stroke volume index (r = 0.1) and heart rate (r = 0.32) were poorly correlated. The combined hemodynamic variables that correlated most closely with MVO2 were the tension/time indices modified by Bretschneider (Psyst x square root (HR)) and Robinson (Psyst x HR x ta) (r = 0.72). Production and consumption of lactate were not correlated with myocardial oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)     

The conundrum of the effect of beta-blockade on myocardial oxygen consumption

The effect of propranolol on myocardial oxygen consumption was studied in in situ canine hearts. In 12 afterload independent isovolumic hearts propranolol increased MVO2 an average of 19 +/- 3% (P less than 0.01) for all peaked developed pressure intervals from 75 to 175 mm Hg, secondary to increased wall stress. In 10 hearts instrumented for computer acquisition of pressure-volume workloops during progressive volume loading on right heart bypass, propranolol decreased preload recruitable stroke work an average of 36% (P less than 0.05). However, propranolol failed to decrease the amount of oxygen consumed for basal metabolism or external mechanical work when MVO2 is indexed for heart rate, heart weight, and stroke work. Therefore, propranolol does not decrease MVO2 for individual contractions and does not affect the energy requirements for basal metabolism, excitation-contraction coupling, and heat generation, in contrast to results obtained with beta agonists.     

Ventricular assist device use with mechanical heart valves: an outcome series and literature review

Background. Management of postcardiotomy cardiogenic shock with a ventricular assist device (VAD) is a common and accepted therapeutic option. However, VAD use in patients with mechanical heart valves (MHVs) is thought to carry an increased risk of thromboembolus. We report a series of 7 patients with combined VAD-MHV and review the literature.

Methods. A retrospective review was performed on all patients who were supported with a ventricular assist device with a mechanical heart valve in place. A literature review was also performed from 1966 to 2000.

Results. Seven patients were identified from April 1988 to June 2000 as having VAD support with a MHV. One thromboembolic event was documented in the 7 patients (14%). Five of the 7 patients (71%) underwent VAD explantation. Overall survival rate was 3 of 7 (43%). Causes of death included heart failure, renal failure, multisystem organ failure, adult respiratory distress syndrome, and cerebral hypoxia. All patients who died had support withdrawn at the request of the family. All patients discharged are currently alive with length of survival of 3, 26, and 84 months.

Conclusions. This study suggests that this population’s rate of survival to discharge and risk of thromboembolus compare favorably to that of the general VAD population. We believe that anticoagulation can be managed as with any MHV patient and that flow rates can be kept slightly lower, which may encourage valve washing.     

Relationship between total mechanical energy and oxygen consumption in the stunned myocardium

We studied the relationship between left ventricular oxygen consumption (LVVO2) and total ventricular mechanical energy production as determined by calculation of the systolic pressure-volume area (P-VA) before and after 25 minutes of warm ischemia in 7 sheep. We compared the relationship between LVVO2 and P-VA with the relationships between LVVO2 and stroke work and between LVVO2 and the systolic stress integral. Using the methods presented, P-VA can be measured in vivo (n = 123) in both preischemic and postischemic hearts. Ischemia increases the slopes of the relationship between LVVO2 and P-VA and between stroke work and the systolic stress integral, and reduces the oxygen utilization efficiency of stroke work to less than 2%. Coefficients of determination for the relationship between LVVO2 and P-VA are, in general, higher than those between LVVO2 and either stroke work or the systolic stress integral. We conclude that systolic P-VA can be measured in vivo using recently developed methods and that it is applicable to postischemic "stunned" hearts. Because P-VA and LVVO2 can be converted into identical energy units, calculation of P-VA permits calculation of myocardial oxygen utilization efficiency.     

Effect of hypothermia and cardioplegia on intramyocardial voltage and myocardial oxygen consumption

Intramyocardial voltage and myocardial oxygen consumption were measured in the fibrillating heart between the temperatures of 37 degrees C and 25 degrees C and in the arrested heart after infusion of potassium cardioplegic solution in 10 adult mongrel dogs. Electrical activity from the myocardium was recorded using specially designed plunge electrodes, and intramyocardial voltage was monitored by an in-line voltmeter. Myocardial oxygen consumption gradually decreased from 5.8 +/- 0.6 ml O2/min at 37 degrees C to 2.3 +/- 0.5 ml O2/min at 25 degrees C. In contrast, hypothermia did not cause a similar decrease in intramyocardial voltage which remained within a range of 1.8 +/- 0.5 mV to 2.4 +/- 0.5 mV between the temperatures of 37 degrees C and 25 degrees C. The infusion of potassium cardioplegic solution resulted in a dramatic decrease in voltage to 43 +/- 5 microV, and myocardial oxygen consumption fell to 0.5 +/- 0.3 ml O2/min. Our data demonstrated that the mean voltage of the fibrillating heart remains constant between the temperatures 37 degrees C and 25 degrees C and myocardial oxygen consumption decreases with hypothermia, which suggests that voltage does not correlate with the level of myocardial oxygen consumption. Myocardial oxygen consumption and intramyocardial voltage, however, decrease dramatically when cardioplegia is instituted.