Glenn J.R. Whitman

Diagnosis and therapeutic evaluation of a pediatric case of cardiomyopathy using phosphorus-31 nuclear magnetic resonance spectroscopy.

An 8 month old girl presented with undiagnosed non-anatomic congenital cardiomyopathy with massive cardiomegaly on chest X-ray film. Her older sibling had died suddenly at 6 months of age from what appeared to be a similar abnormality. Utilizing phosphorus-31 nuclear magnetic resonance (P-31 NMR) surface coil spectroscopy, a metabolic disorder was demonstrated in both her myocardium and skeletal muscle, revealing a phosphocreatine (PCr) to inorganic phosphate (Pi) ratio of half of that for a normal control infant. Manipulation of serum substrate availability indicated that medium chain triglycerides alone did not improve myocardial metabolism, but that intravenous glucose or oral carbohydrate loading raised the myocardial PCr/Pi ratio from 1.0 +/- 0.05 to 1.8 +/- 0.1 (p less than 0.01) without significantly affecting the PCr/Pi value of her resting skeletal muscle. This study demonstrates the feasibility of using P-31 nuclear magnetic resonance to evaluate the biochemistry of the human myocardium in vivo and to diagnose a metabolic abnormality. Phosphorus-31 nuclear magnetic resonance can thus be used to optimize therapy for human disease.

Coenzyme Q10 protects coronary endothelial function from ischemia reperfusion injury via an antioxidant effect

BACKGROUND Cardiac ischemia reperfusion (I/R) injury causes coronary vascular dysfunction. Coenzyme Q10 (CoQ), which preserves cardiac mechanical function after I/R, recently has been recognized as a free radical scavenger. We hypothesized that CoQ protects coronary vascular reactivity after I/R via an antioxidant mechanism. METHODS Rats were pretreated with either CoQ (20 mg/kg intramuscular and 10 mg/kg intraperitoneal [CoQ group]) or a vehicle (Control) before the experiment. Isolated perfused rat hearts were subjected to 25 minutes of global normothermic ischemia and 40 minutes of reperfusion. The reperfusion-induced oxidative burst was directly assessed by lucigenin enhanced chemiluminescence. Coronary flow was measured at equilibration and after reperfusion with or without bradykinin, an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator. The effect of intracoronary infusion of hydrogen peroxide (H2O2 0.1 mumol/gm body weight given over 5 minutes), simulating the free radical burst after I/R, also was evaluated. RESULTS I/R decreased the bradykinin-induced change in coronary flow (-5% +/- 4% versus 26% +/- 3% at equilibration; p < 0.05) and the SNP-induced change (+20% +/- 6% versus +56% +/- 5% at equilibration; p < 0.05). The coronary vasculature after H2O2 infusion revealed a similar loss in vasodilatory responsiveness (+4% +/- 4% in response to bradykinin, +35% +/- 8% in response to SNP; p < 0.05 versus equilibration). Pretreatment with CoQ improved BK-induced vasorelaxation after I/R (+12% +/- 2%; p < 0.05 versus control I/R) or H2O2 infusion (18% +/- 4%; p < 0.05 versus control I/R) but failed to improve SNP-induced vasorelaxation. The CoQ pretreatment decreased the I/R-induced maximal free radical burst (9.3 +/- 0.8 x 10(3) cpm versus 11.5 +/- 1.1 x 10(3) cpm; p < 0.05) during the early period of reperfusion. CONCLUSIONS Endothelium-dependent vasorelaxation is more sensitive than endothelium-independent relaxation to I/R injury. Via a direct antioxidant effect, CoQ preserved endothelium-dependent vasorelaxation by improving tolerance to I/R injury.

Elucidation of a tripartite mechanism underlying the improvement in cardiac tolerance to ischemia by coenzyme Q10 pretreatment

Coenzyme Q10, which is involved in mitochondrial adenosine triphosphate production, is also a powerful antioxidant. We hypothesize that coenzyme Q10 pretreatment protects myocardium from ischemia reperfusion injury both by its ability to increase aerobic energy production and by protecting creatine kinase from oxidative inactivation during reperfusion. Isolated hearts (six per group) from rats pretreated with either coenzyme Q10, 20 mg/kg intramuscularly and 10 mg/kg intraperitoneally (treatment) or vehicle only (control) 24 and 2 hours before the experiment were subjected to 15 minutes of equilibration, 25 minutes of ischemia, and 40 minutes of reperfusion. Developed pressure, contractility, compliance, myocardial oxygen consumption, and myocardial aerobic efficiency were measured. Phosphorus 31 nuclear magnetic resonance (31P-NMR) spectroscopy was used to determine adenosine triphosphate and phosphocreatine concentrations as a percentage of a methylene diphosphonic acid standard. Hearts were assayed for myocardial coenzyme Q10 and myocardial creatine kinase activity at end equilibration and at reperfusion. Treated hearts showed higher myocardial coenzyme Q10 levels (133 +/- 5 micrograms/gm ventricle versus 117 +/- 4 micrograms/gm ventricle, p < 0.05). Developed pressure at end reperfusion was 62% +/- 2% of equilibration in treatment group versus 37% +/- 2% in control group, p < 0.005. Preischemic myocardial aerobic efficiency was preserved during reperfusion in treatment group (0.84 +/- 0.08 mm Hg/(microliter O2/min/gm ventricle) vs 1.00 +/- 0.08 mm Hg/(microliter O2/min/gm ventricle) at equilibration, p = not significant), whereas in the control group it fell to 0.62 +/- 0.07 mm Hg/(microliter O2/min/gm ventricle, p < 0.05 vs equilibration and vs the treatment group at reperfusion. Treated hearts showed higher adenosine triphosphate and phosphocreatine levels during both equilibration (adenosine triphosphate 49% +/- 2% for the treatment group vs 33% +/- 3% in the control group, p < 0.005; phosphocreatine 49% +/- 3% in the treatment group vs 35% +/- 3% in the control group, p < 0.005) and reperfusion (adenosine triphosphate 18% +/- 3% in the treatment group vs 11% +/- 2% in the control group, CTRL p < 0.05; phosphocreatine 45% +/- 2% in the treatment group vs 23% +/- 3% in the control group, p < 0.005). Creatine kinase activity in treated hearts at end reperfusion was 74% +/- 3% of equilibration activity vs 65% +/- 2% in the control group, p < 0.05). Coenzyme Q10 pretreatment improves myocardial function after ischemia and reperfusion. This results from a tripartite effect: (1) higher concentration of adenosine triphosphate and phosphocreatine, initially and during reperfusion, (2) improved myocardial aerobic efficiency during reperfusion, and (3) protection of creatine kinase from oxidative inactivation during reperfusion.

Case 6-5-1992 Anesthetic considerations for thoracoscopic procedures

Cm! 1 A 77-year-old white man was admitted with a left-sided pleura1 effusion. His past history included prolonged asbestos exposure and heavy smoking. He presented with dyspnea and wcight 10s~. Physical examination revealed a thin individual with a large barrel-shaped chest. Preoperative pulmonary function tests showed an FEVt of 1.2 L. A computerized tomography scan showed multiple pleura1 plaques and areas of thickening, especially along the mediastinal pleura. Because of the patient’s poor pulmonary status, flexible bronchoscopy and thoracoscopy were scheduled. The planned perioperative monitoring included indwelling arterial pressure, end-tidal CO1 (ETCO& and peripheral oxygen saturation (SpO

Impact of respiratory acid-base status in patients with pulmonary hypertension

Anesthesia was induced with thiamylal, fentanyl, and vecuronium. The trachea was intubated initially with a single-lumen endotracheal tube for flexible fiberoptic bronchoscopy. Following this, a double-lumen right-sided endobronchial tube was inserted. After confirmatory chest auscultation and flexible bronchoscopy, the patient was positioned in the right lateral decubitus position. Anesthetic maintenance included fentanyl, vecuronium, and isoflurane/air/oxygen. One-lung ventilation (OLV) was maintained during the thoracoscopic procedure. During diagnostic thoracoscopy, the stopcock of the cannula was left open to room air to maintain an open pneumothorax. Air insufflation pressures of 10 to 11 mmHg were used to attain better visibility. Hemodynamic monitoring and management included special attention to changes in blood pressure, heart rate and rhythm, end-tidal CO2 because of the potential for arrhythmias, fa11 in venous return and cardiac output, gas embolism, and direct compression of cardiac structures. The surgical procedure involved multiple pleura1 biopsies and

Albumin decreases hydrogen peroxide and reperfusion injury in isolated rat hearts

BACKGROUND The perioperative management of patients undergoing mitral valve replacement (MVR) with pulmonary hypertension from mitral stenosis may be complicated by increased pulmonary vascular resistance. The purpose of this study was to examine the influence of respiratory acid-base status on the pulmonary hemodynamic indices of patients with pulmonary hypertension before and after MVR. METHODS Ten patients with pulmonary hypertension from mitral stenosis (mean preoperative systolic pulmonary artery pressure, 73 +/- 8 mm Hg) undergoing MVR were studied in the operating room before and after MVR. Arterial partial pressure of carbon dioxide was manipulated by the addition of 5% carbon dioxide to the breathing circuit. Hemodynamic data were collected as the partial pressure of carbon dioxide rose from 30 mm Hg to 50 mm Hg and decreased back to 30 mm Hg. RESULTS There were no differences in mean pulmonary artery pressure or pulmonary vascular resistance before and after MVR. Before MVR, mean pulmonary artery pressure increased from 32 +/- 1 mm Hg to 48 +/- 1 mm Hg as the partial pressure of carbon dioxide rose from 30 mm Hg to 50 mm Hg (p < 0.05), and pulmonary vascular resistance rose from 379 +/- 30 to 735 +/- 40 dynes.second.cm-5 (p < 0.05). These effects on mean pulmonary artery pressure and pulmonary vascular resistance were not different after MVR. CONCLUSION Respiratory acid-base status has a profound impact upon pulmonary vascular resistance in patients with pulmonary hypertension from mitral stenosis undergoing MVR. This impact persists in the immediate postoperative period. We conclude that respiratory acidemia should be avoided in these patients, whereas respiratory alkalemia may be used to help minimize pulmonary vascular resistance.

Postoperative critical care of the adult cardiac surgical patient. Part I: Routine postoperative care

Perfusion with human serum albumin decreased myocardial hydrogen peroxide (H2O2) levels (as assessed by inactivation of myocardial catalase activities following ammotriazole pretreatment) and increased myocardial ventricular developed pressures (DP), contractility (+dP/dt) but not relaxation rate (-dP/dt) in isolated crystalloid perfused rat hearts subjected to normothermic global ischemia (20 min) and then reperfusion (40 min). Albumin also decreased H2O2 concentrations in vitro. The findings support the possibility that albumin may act as a protective O2 metabolite scavenger in vivo.

The relationship between global myocardial ischemia, left ventricular function, myocardial redox state, and high energy phosphate profile. A phosphorous-31 nuclear magnetic resonance study☆

Objectives:Cardiac surgery, including coronary artery bypass, cardiac valve, and aortic procedures, is among the most common surgical procedures performed in the United States. Successful outcomes after cardiac surgery depend on optimum postoperative critical care. The cardiac intensivist must have a comprehensive understanding of cardiopulmonary physiology and the sequelae of cardiopulmonary bypass. In this concise review, targeted at intensivists and surgeons, we discuss the routine management of the postoperative cardiac surgical patient. Data Source and Synthesis:Narrative review of relevant English-language peer-reviewed medical literature. Conclusions:Critical care of the cardiac surgical patient is a complex and dynamic endeavor. Adequate fluid resuscitation, appropriate inotropic support, attention to rewarming, and ventilator management are key components. Patient safety is enhanced by experienced personnel, a structured handover between the operating room and ICU teams, and appropriate transfusion strategies.

Evaluation of myocardial preservation using 31P NMR

UNLABELLED The onset of global myocardial ischemia was related to mechanical function (intraventricular pressure), cellular redox state (NADH fluorophotography), and high energy profile (phosphorous-31 nuclear magnetic resonance). Ten rabbit hearts were excised and perfused on a modified Langendorff apparatus (37 degrees C; pO2 480 Torr). Developed pressure and positive and negative dp/dt were determined at control, 1-10, 15, 30, 45, and 60 sec of acute global ischemia. NADH fluorophotographs were taken at control, 1-10, 15, 20, 30, 60 sec, and 5, 10, and 30 min. P-31 NMR spectra in 14 guinea pig hearts under identical conditions were obtained at control, 1, 5, 10, 20, 40, and 60 min of acute global ischemia. LV contractility diminished within 1 sec (P less than 0.01) of ischemia and dropped to less than 35% of control by 1 min. Reduction of mitochondria was detected by epicardial NADH fluorophotography at 2 sec of ischemia. Cellular pH diminished 0.3 pH units by 5 min. Adenosine triphosphate (ATP) concentration remained at control levels while phosphocreatine (PCr) dropped to 63 +/- 8.5% of control by 1 min of ischemia. CONCLUSIONS After the onset of global ischemia (1) mitochondrial electron transport ceases by 2 sec; (2) acidosis develops immediately; (3) LV contractility diminishes by 1 sec; (4) ATP concentration appears to be buffered by PCr, and is dissociated from myocardial function.

Infected biatrial myxoma: Transesophageal echocardiography-guided surgical resection

The purpose of this study was (1) to monitor myocardial high-energy phosphate content and recovery of left ventricular (LV) contractile function following normothermic graded cardiac ischemia and single-dose hypothermic potassium cardioplegia, and (2) to assess the temporal limits of LV functional recovery during single-dose cardioplegia maintained at 17 degrees C. Rabbit hearts (30) were perfused, equipped with an LV balloon, paced at 240 beats/min, and placed in a nuclear magnetic resonance (NMR) magnet. Hearts underwent either graded, global normothermic ischemia or potassium cardioplegia arrest maintained at 17 degrees C for 1 hr. Myocardial high-energy phosphate level, LV contractility, and temperature were monitored continuously. Phosphocreatine (PCr) fell to 10 +/- 2, 2 +/- 1, and 0% of control and ATP to 70 +/- 3, 19 +/- 7, and 0% of control at 10, 40, and 60 min of 37 degrees C ischemia. After 1 hr of reperfusion, regression analysis of final developed pressure (DP) on end ischemic ATP (EIATP) content revealed: DP = 1.02 EIATP + 18 (r = 0.95). Following single-dose cardioplegia, maintained at 17 degrees C, PCr fell to 16 +/- 3% of control at 60 min while ATP fell only to 92 +/- 5% control. With reperfusion, recovery of DP was 100%. It was concluded that (1) PCr serves as an energy buffer for ATP, (2) EIATP predicts recovery of LV function, (3) single-dose cardioplegia maintained at 17 degrees C provides complete myocardial preservation for up to 60 min.