Coronary Sinus Lactate Concentration Research Articles

(735) - Impact of Initial Acidic Reperfusion on the Functional Recovery of DCD Hearts During Ex Vivo Heart Perfusion

s S251 normothermic beating state and transitioned into working mode for assessment of myocardial function by measuring the cardiac index (mL/minute/gram heart tissue) achieved at a left atrial pressure of 8 mmHg and an aortic diastolic pressure of 40 mmHg. RESULTS: Hearts sustained an equivalent period of warm ischemia (5 C1⁄428 1, 25 C1⁄429 1, 35 C1⁄427 1 minutes, p1⁄40.50) prior to IR. During IR coronary blood flow (5 C1⁄4483 53, 25 C1⁄4722 60, 35 C1⁄4906 36 mL/min, p<0.01) and coronary sinus lactate concentration (5 C1⁄4 0.73 0.06, 25 C1⁄41.33 0.03, 35 C1⁄41.75 0.15 umol/L, p<0.01) differed among treatment groups. Greater preservation of endothelial cell integrity (electron microscopy endothelial injury score: 5 C1⁄43.2 0.5, 25 C1⁄41.8 0.2, 35 C1⁄41.7 0.3, p1⁄40.01) and less myocardial injury (troponin I: 5 C1⁄491 6, 25 C1⁄464 16, 35 C1⁄457 7 pg/ mL/gram, p1⁄40.04) were evident in hearts reperfused at warmer temperatures. IR under profoundly hypothermic conditions impaired the recovery of indexed cardiac output (5 C1⁄43.9 0.8, 25 C1⁄46.2 0.4, 35 C1⁄46.5 0.0.6 mL/min/ gram, p<0.01). CONCLUSION: Avoidance of profound hypothermia during IR with a normokalemic adenosine-lidocaine cardioplegia minimizes injury and improves the functional recovery of DCD hearts. 384 GENDER SPECIFIC INFLUENCES ON EFFECTOR T-CELL FUNCTION AND PROLIFERATION: 2-METHOXYESTRADIOL MODULATES CELLULAR REJECTION JG Luc, JY Zhao, ED Michelakis, DH Freed, J Nagendran

IMPACT OF INITIAL ACIDIC REPERFUSION ON THE FUNCTIONAL RECOVERY OF DCD HEARTS DURING EX VIVO HEART PERFUSION

Donor hearts following circulatory death (DCD) have been proposed as an alternative source of organs for transplant. DCD hearts experience significant ischemia during the hypoxemic cardiac arrest and warm-ischemic standoff period that ethically define death. Subsequent initial reperfusion (IR) causes intracellular sodium and calcium overload, which play an important role in the pathogenesis of ischemia-reperfusion injury. However, initial acidic reperfusion may minimize sodium and calcium overload, limit ischemia-reperfusion injury, and optimize functional recovery. We investigated the impact of IR pH on the recovery of myocardial function during ex vivo heart perfusion (EVHP). Twenty-two pigs were anesthetized, mechanical ventilation was discontinued, and cardiac arrest ensued. A 15-minute warm-ischemic standoff period was observed and then hearts were procured and reperfused with an oxygenated, normokalemic, adenosine-lidocaine, cardioplegia with a pH of 6.4 (N=6), 6.9 (N=8), or 7.4 (N=8) for 3 minutes at 35°C. Hearts were then perfused ex vivo in a normothermic beating state and transitioned into working mode for assessment of myocardial function by measuring the cardiac index (mL/minute/gram heart tissue) achieved at a left atrial pressure of 8 mmHg and an aortic diastolic pressure of 40 mmHg. Hearts sustained an equivalent period of warm ischemia (6.4=27.0±0.7, 6.9=27.5±0.3, 7.4=27.9±0.4 minutes, p=0.39) prior to IR. Coronary blood flow (6.4=910±21, 6.9=871±31, 7.4=868±34 mL/min, p=0.60) and coronary sinus lactate concentration (6.4=1.6±0.5, 6.9=1.3±0.1, 7.4=1.9±0.1 umol/L, p=0.25) were comparable among treatment groups during IR. The pH of the cardioplegic solution delivered during the 3-minute IR period significantly impacted the development of myocardial edema (6.4=15.2±2.9, 6.9=8.5±1.2, 7.4=10.1±0.9 grams/hour weight gain, p=0.03) and the recovery of indexed cardiac output (6.4=3.1±0.8, 6.9=8.4±1.8, 7.4=6.1±0.9 mL/minute/gram, p=0.04) during subsequent EVHP. IR of DCD hearts with a profoundly acidic (pH=6.4) cardioplegic solution is associated with the development of myocardial edema and impaired functional recovery during EVHP, while IR under moderately acidic (pH=6.9) conditions appears to be protective.

AVOIDANCE OF PROFOUND HYPOTHERMIA DURING INITIAL REPERFUSION IMPROVES THE FUNCTIONAL RECOVERY OF DCD HEARTS

s S251 normothermic beating state and transitioned into working mode for assessment of myocardial function by measuring the cardiac index (mL/minute/gram heart tissue) achieved at a left atrial pressure of 8 mmHg and an aortic diastolic pressure of 40 mmHg. RESULTS: Hearts sustained an equivalent period of warm ischemia (5 C1⁄428 1, 25 C1⁄429 1, 35 C1⁄427 1 minutes, p1⁄40.50) prior to IR. During IR coronary blood flow (5 C1⁄4483 53, 25 C1⁄4722 60, 35 C1⁄4906 36 mL/min, p<0.01) and coronary sinus lactate concentration (5 C1⁄4 0.73 0.06, 25 C1⁄41.33 0.03, 35 C1⁄41.75 0.15 umol/L, p<0.01) differed among treatment groups. Greater preservation of endothelial cell integrity (electron microscopy endothelial injury score: 5 C1⁄43.2 0.5, 25 C1⁄41.8 0.2, 35 C1⁄41.7 0.3, p1⁄40.01) and less myocardial injury (troponin I: 5 C1⁄491 6, 25 C1⁄464 16, 35 C1⁄457 7 pg/ mL/gram, p1⁄40.04) were evident in hearts reperfused at warmer temperatures. IR under profoundly hypothermic conditions impaired the recovery of indexed cardiac output (5 C1⁄43.9 0.8, 25 C1⁄46.2 0.4, 35 C1⁄46.5 0.0.6 mL/min/ gram, p<0.01). CONCLUSION: Avoidance of profound hypothermia during IR with a normokalemic adenosine-lidocaine cardioplegia minimizes injury and improves the functional recovery of DCD hearts. 384 GENDER SPECIFIC INFLUENCES ON EFFECTOR T-CELL FUNCTION AND PROLIFERATION: 2-METHOXYESTRADIOL MODULATES CELLULAR REJECTION JG Luc, JY Zhao, ED Michelakis, DH Freed, J Nagendran

Initial Reperfusion of DCD Hearts Under Hypothermic Conditions Impairs Myocardial Functional Recovery During Ex Vivo Heart Perfusion.

Objective: Initial reperfusion (IR) of donor hearts following circulatory death (DCD) with cardioplegia may facilitate restoration of ion homeostasis prior to myocardial contraction, minimize ischemia-reperfusion injury, and optimize functional recovery. We investigated the impact of IR temperature on the recovery of myocardial function during ex vivo heart perfusion. Methods: Eighteen pigs were anesthetized, mechanical ventilation was discontinued, and cardiac arrest ensued. A 15-minute standoff period was observed and then hearts were procured and reperfused with a normokalemic adenosine-lidocaine crystalloid cardioplegia for 3 minutes at 3 different temperatures (5°C; N=6, 25°C; N=5, and 35°C; N=7). Hearts were then perfused ex vivo in a normothermic beating state and transitioned into working mode (left atrial pressure: 8 mmHg) at 1, 3, and 5 hours for assessment of myocardial function using a conductance catheter. Results: Hearts sustained an equivalent period of warm ischemia (5°C=28±1, 25°C=29±1, 35°C=27±1 minutes, p=0.50) prior to IR. IR coronary blood flow (5°C=483±53, 25°C=722±60, 35°C=906±36 mL/min, p<0.01) and coronary sinus lactate concentration (5°C=0.73±0.06, 25°C=1.33±0.03, 35°C=1.75±0.15 umol/L, p<0.01) differed among treatment groups. IR under hypothermic conditions impaired systolic (dP/dt max) and diastolic (dP/dt min) functional recovery (Figure 1). Electron microscopy revealed greater preservation of endothelial cell integrity in hearts reperfused at warmer temperatures (injury score 5°C=3.2±0.5, 25°C=1.8±0.2, 35°C=1.7±0.3 minutes, p=0.01). Conclusions:Avoidance of profound hypothermia during IR with an adenosine-lidocaine cardioplegia preserves endothelial integrity and improves the functional recovery of DCD hearts.Figure: No Caption available.

Use of continuous retrograde gaseous oxygen persufflation for myocardial protection during open heart surgery

The infusion of a cardioplegic solution is the standard method of myocardial protection during open heart surgery. However, this method interrupts the surgical procedure and it is difficult to ensure a bloodless surgical field. To address these problems, the effect of continuous retrograde gaseous oxygen persufflation (ROP) on myocardial protection was assessed in comparison to St. Thomas' solution (STS). Eighteen adult mongrel dogs were divided into three groups of six. Group G received continuous ROP, Group C received STS every 30 min, and Group N received hypothermia alone during the 120 min hypothermic ischemia. The myocardial metabolism was assessed by measuring the coronary sinus lactate concentration, lactate extraction ratio (LER), coronary sinus lipid peroxidation (LPO) concentration, left ventricular myocardial adenosine triphosphate (ATP) concentration, and water content. Cardiac function was assessed by the percent recovery relative to the baseline. In Group G, the lactate, LPO, and water content were significantly lower (P = 0.0062, P = 0.03, and P = 0.0065, respectively), and ATP was significantly higher (P = 0.028) than in Group C. The LER was only positive in Group G. In addition, the cardiac functions in Groups G and C were not significantly different. Retrograde gaseous oxygen persufflation was not inferior to STS in regard to myocardial protection. This technique could therefore represent a potentially promising cardioplegic method.

Coronary sinus lactate concentration during myocardial reperfusion

Coronary sinus lactate concentration during myocardial reperfusion

Nitroglycerin-induced hypoxemia does not produce myocardial ischemia

Objective: Nitroglycerin has been the drug of choice for relieving myocardial ischemia for more than a hundred years. Several studies have indicated that a significant reduction in arterial oxygen tension (PaO 2) occurs after the administration of sublingual nitroglycerin to patients with coronary artery disease breathing room air. Because available oxygen in arterial blood is reduced, it would be reasonable to assume that oxygen delivery to the myocardium would also be impaired. The purpose of this study was to investigate whether nitroglycerin-induced arterial desaturation results in compromised oxidative metabolism of myocardium assessed by coronary sinus lactate concentration and oxygen content in patients with coronary artery disease undergoing coronary artery bypass surgery. Participants: Ten randomly selected patients undergoing coronary bypass surgery. Setting: All studies were performed at Siyami Ersek Cardiovascular and Thoracic Surgery Center. Methods: A catheter was inserted into the radial artery to measure blood gases and arterial lactate concentration. After sternotomy, and aortic and venous cannula placement, a coronary sinus catheter was introduced into the coronary sinus to measure oxygen content and lactate concentration. Control coronary sinus and arterial blood samples were obtained before nitroglycerin infusion. Nitroglycerin was then given in a dose of 2 μg/kg/min for a period of 5 minutes. At the end of 5 minutes, second samples were obtained from the coronary sinus and arterial catheters. Main Results: It was found that arterial and coronary sinus oxygen tension decreased significantly. Arterial lactate concentration did not change, coronary sinus lactate concentration decreased. Despite a substantial fall in arterial oxygen tension after administration of nitroglycerin, a significant reduction in coronary sinus lactate concentration occurred. Conclusion: Nitroglycerin-induced hypoxia does not compromise oxidative metabolism of myocardium as can be assessed by a concomitant decrease in coronary sinus lactate concentration.

Dichloroacetate Enhanced Myocardial Functional Recovery Post-ischemia: ATP and NADH Recovery

This study was undertaken to determine the effect of dichloroacetate (DCA) on myocardial functional and metabolic recovery following global ischemia. Isolated rabbit hearts were subjected to 120 min of mildly hypothermic (34°C), cardioplegic arrest with multidose, modified St. Thomas’ cardioplegia. Hearts were reperfused with either physiologic salt solution (PSS) as controls, (CON,n= 10) or PSS containing DCA (DCA,n= 6) at a concentration of 1 mM.Functional and metabolic indices were determined at baseline and at 15, 30, and 45 min of reperfusion. In four DCA and four CON hearts, myocardial biopsies were taken at baseline, end-ischemia, 15 and 45 min for nucleotide levels. Functional recovery was significantly better in hearts reperfused with DCA as demonstrated by recovery of baseline developed pressure (DCA = 69 ± 5%, CON = 45 ± 9%) and dP/dt (DCA = 64% ± 10% versus CON = 48% ± 10%). Coronary blood flow was not different between groups either at baseline or during reperfusion, but myocardial oxygen consumption (MVO2) was increased in the DCA versus CON hearts (79% ± 20% of baseline vs 50% ± 18%). Recovery of myocardial adenylate energy status was improved in the DCA versus CON hearts (ATP recovered to 45% ± 20% versus 8% ± 6% of baseline). Coronary sinus lactate concentration was decreased in DCA perfused hearts at 45 min of reperfusion. Percent of baseline NADH values was similar at 15 min of reperfusion, but at 45 min, DCA hearts showed a decrease in NADH levels, while CON hearts showed an increase (DCA = 48%; CON = 121%). The enhanced myocardial function and improved metabolic status noted with DCA may result from increased oxidative phosphorylation due to altered pyruvate dehydrogenase (PDH) activity.

Perioperative assessment of cardiac energy metabolism by means of arterio-coronary venous difference in lactate concentration (acDL) A parameter for optimizing ventricular function of the postcardioplegic myocardium

Fourty-three patients undergoing open heart surgery were subjected to extended hemodynamic and metabolic monitoring (arterial and coronary sinus (CS) lactate concentration). In 95% of patients investigated, a significant increase in CS lactate concentration above the arterial lactate concentration was established at the beginning of reperfusion (RPT). In these cases, a decrease in the CS lactate below the arterial concentration occurs within the RPT creating a cross-over point (COP) from negative to positive lactate extraction values. Whereas the initial rise in CS lactate is an expression of the expected ischemia-induced acceleration of anaerobic glycolysis, the onset of a positive lactate extraction can be related to reconsolidation of mitrochondrial oxidative phosphorylation. We found two groups with an early and late COP at 7.2 +/- 0.8 min (ECOP) and 42.5 +/- 5.2 min (LCOP) (P less than 0.005). Whereas a short cross-over time was associated with a normal postoperative outcome, cardiac recovery was delayed in the LCOP group. With the aid of metabolic monitoring it is possible to identify the COP and cardiac overload situations and so to optimize the perioperative outcome, especially in selected patients (NYHA stage III/IV, re-operation, high-risk operation).

Increased coronary sinus lactate concentration during pacing induced angina pectoris after clinical improvement by glyceryl trinitrate.

Ten patients with stable angina pectoris and obstructed coronary arteries (greater than 75% reduction in diameter) were studied before and during two periods of pacing, the second of which was preceded by sublingual administration of glyceryl trinitrate (mean dose 0.78 mg). Coronary sinus blood flow measurements and aortocoronary sinus blood sampling for metabolite determinations were carried out. Although the rate of pacing was increased by 10 beats/minute after glyceryl trinitrate administration, the onset of angina was delayed in eight patients during pacing. Drug administration decreased coronary sinus blood flow by 42% and myocardial oxygen uptake by 41% during pacing and induced a shift in mean lactate extraction towards a net release (from 3.1% to -12.6%). It increased the number of patients producing lactate from three to five. Glyceryl trinitrate administration decreased myocardial glucose uptake throughout the study, decreased lactate extraction during recovery, and increased the aortocoronary sinus citrate gradient at rest and during recovery, while the exchange of free fatty acids remained unchanged. A decrease in aortocoronary sinus lactate difference during pacing after glyceryl trinitrate administration correlated positively with the fall in coronary sinus blood flow. The metabolic data do not indicate an augmented myocardial lactate production after glyceryl trinitrate administration. A decrease in coronary sinus blood flow seems, therefore, to be of primary importance in explaining the elevated coronary sinus lactate concentration. Our finding that coronary sinus lactate concentration increased during pacing after glyceryl trinitrate administration despite clinical improvement questions the validity of its use as a quantitative index of ischaemia.