Biomedical subjects

D A Mickle

Publications and source records attributed to D A Mickle.

At least 109 records · Page 6Linked to original sources

PubMed1987

The effect of low-flow cardiopulmonary bypass on cerebral function: an experimental and clinical study.

Systemic flow rates (Q) during nonpulsatile hypothermic cardiopulmonary bypass (CPB) that are consistent with preservation of cerebral function have not to our knowledge been objectively defined. The effect of a sequential reduction in flow rates on cerebral cortical metabolism and function was evaluated in 6 mongrel dogs during hypothermic (25 degrees C) CPB. Cerebral function was assessed using somatosensory cortical evoked potentials (SSEP); cerebral metabolism was assessed by adenosine triphosphate (ATP) and lactate content of snap-frozen gray matter biopsies taken from the hemisphere contralateral to that monitored for SSEP. A progressive decline in ATP levels was observed during flow reduction with virtually complete depletion of ATP at 0.25 L min-1 m-2(p = .0003). The significant (p = .028) dependence of cortical ATP levels on perfusion pressure was no longer evident after adjusting for the effects of flow rate. Lactate levels increased during flow reduction (p = .028), especially at flow rates less than 0.5 L min-1 m-2. Somatosensory neural transmission remained intact until flow was reduced to 0.25 L min-1 m-2 in 5 animals and until total circulatory arrest in 1, at which time loss of the signal occurred. In addition, 5 patients were subjected to brief periods of low-flow CPB (Q = 1.0 L min-1 m-2) at 21 degrees to 25 degrees C. SSEPs remained intact during flow reduction, and postoperative neurologic evaluation was normal in all patients. We conclude that, in the absence of cerebral vascular disease, the flow rate threshold for incurring functional cerebral injury during hypothermic (25 degrees C) nonpulsatile CPB is less than 1.0 L min-1 m-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1987

Conjugated dienes in ischemic and reperfused myocardium: an in vivo chemical signature of oxygen free radical mediated injury.

Free radical reactions have been suggested to be important events in the mechanism of myocardial injury during ischemia and reperfusion. Most of the in vivo evidence implicating free radical mediated events in the etiology of myocardial injury has been based on intervention studies which document the efficacy of oxygen free radical scavengers in improving function or tissue salvage. We have assayed free fatty acid oxidation products (hydroxy conjugated dienes) derived from myocardial phospholipid as chemical markers of oxidative injury. Biopsies, harvested from canine myocardium subjected to cardiopulmonary bypass with no aortic crossclamp (control), from pre-ischemic, end ischemic (at the end of 45 min of global normothermic ischemia induced by aortic crossclamp) and at 5, 10, 15, 30 and 60 mins of reperfusion were analyzed for hydroxy conjugated dienes using HPLC with structural confirmation by GC-MS. All biopsies were taken from non-necrotic myocardium as indicated by gross tetrazolium staining of myocardial cross sections. Trace levels of hydroxy conjugated dienes could be detected in the preischemic biopsies or control biopsies harvested from hearts subjected to cardiopulmonary bypass with no ischemia. At the end of 45 min ischemia, however, a significant increase in 18:2 and 20:4 hydroxy isomers was detected and confirmed by GC-MS (P less than 0.05 vs. control). After 5 mins of reperfusion a further significant increase in hydroxy conjugated dienes was noted with 18:2, 20:4 and 22:6 isomers being identified (P less than 0.01 vs. end ischemia). By 30 min of reperfusion the concentration of phospholipid oxidation products had returned to pre-ischemic levels. This study presents the first chemically rigorous in vivo evidence for the formation of products of phospholipid oxidation (hydroxy conjugated dienes) during myocardial ischemia and reperfusion and supports the concept of oxygen free radical mediated lipid peroxidation. This study emphasizes the formation of phospholipid oxidation products during ischemia and particularly during the early phase of reperfusion and illustrates the transient nature of these products in myocardial phospholipid.

Animals↗

PubMed1987

Salvage of skeletal muscle with free radical scavengers.

Extensive skeletal muscle necrosis may occur after prolonged ischemia to the lower extremity, with serious consequences both locally and systemically. The extent of necrosis is a combination of cellular damage that occurs during both the period of ischemia and the period of reperfusion. The purpose of this study was to reduce the extent of reperfusion-induced muscle necrosis by therapeutic interventions administered only during the initial period of reperfusion. Indeed, the pretreatment of patients who have an acute arterial occlusion is rarely possible and only interventions applicable to the reperfusion phase would be clinically relevant. By perfusing the isolated gracilis muscle in a controlled manner with reduced oxygen concentrations alone and in combination with free radical scavengers, we were able to reduce the extent of muscle necrosis. By means of controlled oxygen delivery alone, muscle necrosis was reduced from 87% +/- 8% in the control muscle to 67% +/- 9% (p less than 0.05) in the treated muscle. The combination of reduced oxygen delivery and free radical scavengers reduced necrosis from 78% +/- 8% in the control muscle to 53% +/- 7% (p less than 0.01) on the experimental side. We conclude that controlled oxygen delivery and free radical scavengers can reduce skeletal muscle necrosis occurring after prolonged normothermic ischemia.

Animals↗

PubMed1987

Impaired left ventricular postischemic function and metabolism in chronic right ventricular hypertrophy.

Chronic right ventricular hypertrophy (RVH) has been shown to produce changes in left ventricular diastolic properties but minimal effects on left ventricular systolic function. We studied the effects of chronic pressure overload RVH on left ventricular systolic function before and after reversible hypothermic global ischemia. RVH was induced by pulmonary artery banding (PAB) in newborn piglets (5 to 7 days). At 2 months of age the PAB group (n = 6) and a control group (n = 8) were subjected to cardiac arrest on cardiopulmonary bypass with cold crystalloid cardioplegia (10 degrees C) for 2 hr and were reperfused for 1 hr. Left ventricular function was assessed by a conductance catheter in the left ventricle measuring the end-systolic pressure-volume relationship (Emax). Preischemic and postischemic Emax were the same in the control group (4.1 +/- 0.4 mm Hg/ml before vs 4.1 +/- 0.4 mm Hg/ml after ischemia), but significantly different in the PAB group (4.7 +/- 0.5 mm Hg/ml before vs 2.97 +/- 0.7 mm Hg/ml after ischemia, p less than .05). There also was a marked drop in ATP and phosphocreatine (CP) content in the PAB group during ischemia (ATP, 20 +/- 2 mmol/kg dry wt before vs 10 +/- 2 mmol/kg dry wt after ischemia, p less than .05; PC, 26 +/- 3 mmol/kg dry wt before vs 11 +/- 1 mmol/kg dry wt after ischemia, p less than .05). In the control group there was no change in ATP content and, although CP did drop by end-ischemia, there was complete recovery by 1 hr of reperfusion but minimal CP recovery in the PAB group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1987

Evidence of myocardial free radical injury during elective repair of tetralogy of Fallot.

Evidence of human myocardial oxygen-mediated free radical injury (OFRI) during cardiovascular repair is lacking. We studied six cyanotic children (ages 3.5 to 5.5 years) during elective repair of tetralogy of Fallot. Right ventricular biopsy specimens, obtained on bypass just before aortic cross-clamping, at the end of 40 +/- 8 min (mean +/- SD) cold arrest with blood cardioplegia, and during reperfusion, were analyzed for hydroxy conjugated dienes, a chemical signature of free radical injury. Structural confirmation of the dienes was done by mass spectroscopy. Conjugated dienes were detected before ischemia on bypass, at end-ischemia, and during reperfusion. The products identified are 9 and 13 OH isomers of linoleic acid and 5, 8, 9, 11, and 15 OH isomers of arachidonic acid. Microscopic examination of right ventricular biopsy specimens obtained on bypass just after cross-clamping showed focal myocyte necrosis. The hydroxy conjugated diene levels in control canine hearts subjected to 105 min of cardiopulmonary bypass without aortic cross-clamping were not detectable. Our results support the occurrence of oxygen-mediated free radical injury during elective repair of tetralogy of Fallot. The presence of conjugated dienes before aortic cross-clamping suggests oxygen toxicity with reoxygenation from cardiopulmonary bypass.

Animals↗

PubMed1987

Atrial activity during cardioplegia and postoperative arrhythmias.

Cardioplegia provides excellent protection for the left ventricle, but the right atrium may be poorly protected. Myocardial temperatures, right atrial electrical activity, and postoperative arrhythmias were assessed in 103 patients participating in two consecutive randomized trials comparing blood cardioplegia (n = 36), crystalloid cardioplegia (n = 38), and diltiazem crystalloid cardioplegia (n = 29). Both right atrial and right ventricular temperatures were significantly warmer (p less than 0.05) during delivery of the blood cardioplegic solution than during delivery of either the crystalloid or the diltiazem crystalloid cardioplegic solutions; the aortic root temperatures were 9 degrees +/- 2 degrees C with blood cardioplegia and 5 degrees + 1 degrees C with both crystalloid and diltiazem crystalloid cardioplegia. Atrial activity during cardioplegic arrest was greatest with blood cardioplegia (12 +/- 3 beats/min), lower with crystalloid cardioplegia (10 +/- 2 beats/min), and minimal with diltiazem crystalloid cardioplegia (5 +/- 1 beats/min, p less than 0.05). Perioperative ischemic injury (by creatine kinase MB isoenzyme analysis) was greatest with crystalloid cardioplegia (p less than 0.05). Postoperative supraventricular arrhythmias (both treated and untreated) were more frequent after crystalloid cardioplegia (crystalloid, 63%; blood, 40%; diltiazem, 47%; p less than 0.05). Patients in whom supraventricular arrhythmias developed had significantly more postoperative ischemic injury (by creatinine kinase MB isoenzyme analysis, p less than 0.05). Blood cardioplegia reduced supraventricular arrhythmias by reducing ischemic injury despite warmer intraoperative temperatures and more right atrial activity. Diltiazem crystalloid cardioplegia reduced postoperative arrhythmias by improving intraoperative myocardial protection and suppressing intraoperative and postoperative atrial activity. Crystalloid cardioplegia cooled but did not arrest the right atrium intraoperatively, resulted in the most perioperative ischemic injury, and yielded the highest incidence of postoperative supraventricular arrhythmias.

Arrhythmias, Cardiac↗

PubMed1987

Age-related differences in the response to myocardial ischemic stress.

Clinical experience indicates that the risk of reparative cardiac operations is increased in the neonatal period relative to that in older infants and children. Age-related differences in the susceptibility to myocardial ischemic dysfunction were evaluated by comparison of left ventricular function and metabolism in neonatal (mean age = 7 days) and weanling (mean age = 96 days) piglets. Six animals in each group supported on cardiopulmonary bypass were subjected to (1) 120 minutes of hypothermic crystalloid cardioplegic arrest (CP-120) and (2) 15 minutes of normothermic ischemic arrest (NA-15) after a 60 minute interval of reperfusion. Left ventricular systolic and diastolic function was measured after each intervention via endocardially implanted ultrasonic dimension crystals in a septolateral minor-axis position. In both groups, systolic dysfunction was evidenced by an increase in the dimension-axis intercept (p = 0.001), but not the slope of the end-systolic pressure-dimension relation. Left ventricular end-diastolic stiffness, expressed as left ventricular end-diastolic pressure versus Lagrangian strain, increased to a similar degree in both groups (p = 0.001). Adenosine triphosphate levels declined significantly (p = 0.001) in both groups in response to the ischemic interventions with no evident intergroup differences. Lactate levels increased significantly during the course of the experiment (p = 0.04); however, the increases were greater (p = 0.009) at all intervals in the neonatal group. This study demonstrates age-related metabolic differences in response to ischemia consistent with a greater dependence on glycolysis in neonatal myocardia. However, the fact that discriminating age-related differences in left ventricular function were not evident suggests that factors other than young age per se account for the increased surgical mortality in the neonatal period.

Adenosine Triphosphate↗

PubMed1986

An isolated skeletal muscle model suitable for acute ischemia studies.

A modified isolated canine gracilis model of acute complete muscle ischemia was developed and then tested metabolically and histologically in 25 animals to assess its validity. In each dog, both gracili were isolated on their major vascular pedicles. One muscle underwent ischemia and reperfusion by placing and removing microvascular clips on the artery and vein. The other gracilis muscle was used as a control. Total muscle blood flow measurements, blood samples, and muscle biopsies were taken every other hour for up to 11 hr after preparation. The fiber-type profile of the gracilis was determined bilaterally using a myosin ATPase stain (n = 10). The results verified these hypotheses: after surgical preparation, the right and left muscles in the same dog are equivalent metabolically, after a 2-hr stabilization period, gracilis blood flow, oxygen and glucose uptake, lactate release, and tissue glycogen, lactate, phosphocreatine, and ATP levels remain within normal limits and unchanged for the next 9 hr, the surgical isolation of the gracilis muscle on a single vascular pedicle does not result in significant metabolic changes, in this model, a 2-hr ischemia is reversible, but a 7-hr ischemia results in irreversible ischemic injury. As well, fiber-type profile, muscle blood flow, and metabolic parameters can very significantly among animals supporting the necessity of a contralateral control. Therefore, this modified gracilis muscle model with its contralateral muscle as a control is suitable for acute skeletal muscle ischemia experiments of at least 9-hr duration.

Adenosine Triphosphate↗

PubMed1986

Exogenous substrate preference of the post-ischaemic myocardium.

Myocardial exogenous substrate preference was studied under conditions of increased plasma lactate concentration before and after a severe (halving of tissue ATP concentration, sixfold increase in tissue lactate concentration) but reversible (less than 1% necrosis on reperfusion) global ischaemic stress produced by continuous hypothermic electromechanical arrest of the heart of four hours' duration by aortic cross clamping and multidose potassium cardioplegia. Fatty acid oxidation was studied using 1-14C-palmitate under steady state conditions and under similar isovolumic fixed pressure conditions with the heart at a constant rate using a left ventricular intracavitary balloon. Exogenous free fatty acid oxidation during the pre-ischaemic period with an increased lactate concentration (3.9-5.8 mmol . litre-1) was 0.62(0.21) mumol . min-1 X 100 g-1 (mean (SEM)). This represented a mean of 32% of the total carbon dioxide produced in contrast to a post-ischaemia free fatty oxidation rate of 2.67(0.87) mumol . min-1 X 100 g-1, in the presence of even further increased plasma lactate concentrations (8.47-11.17 mmol . litre-1), representing a mean of 82% of the total carbon dioxide output. These data suggest that the substrate preference of the myocardium, under conditions of increased plasma lactate concentration, shifts to greater oxidation of exogenous free fatty acids after ischaemic stress.

Adenosine Triphosphate↗

PubMed1986

Metabolic response of skeletal muscle to ischemia.

To evaluate the temporal relationship and potential correlation between intramuscular phosphagen levels, lipid oxidation, and extent of muscle injury, a canine gracilis muscle model was used to study the consequences of a global ischemic episode for up to 7 h duration with reperfusion for 4 h. In this model the contralateral gracilis muscle was prepared identically to the test side but was not subjected to ischemia and thus served as a control. Blood flow, oxygen consumption, and lactate and glycerol release were measured before and after 2- and 7-h ischemic stress periods. The intramuscular metabolites, glycogen, lactate, phosphocreatine, and ATP, as well as free fatty acid conjugated dienes, were measured before, during, and after the ischemic insult. A 2-h ischemic insult resulted in minimal ultrastructural damage and complete regeneration of intramuscular phosphagens and glycogen on reperfusion with complete normalization of lipid oxidation products. In contrast, a 7-h ischemic insult resulted in profound injury at the ultrastructural level with an inability to restore intramuscular phosphagens and glycogen on reperfusion. This severe muscle injury correlated with a 2.5-fold increase in lipid oxidation products (free fatty acid conjugated dienes) and a decline in ATP levels below 5 mumol/g dry wt on reperfusion. Our results emphasize the prolonged glycolytic activity of skeletal muscle during global ischemia and document the increased production of oxygen free radical-mediated lipid oxidation products in irreversibly injured muscle.

Adenosine Triphosphate↗

PubMed1986

Reducing the risk of urgent revascularization for unstable angina: a randomized clinical trial.

A prospective, randomized trial was instituted to determine whether blood cardioplegia (BC) could reduce the morbidity and mortality for patients undergoing urgent coronary bypass for unstable angina. One hundred forty patients who came to the hospital with prolonged angina at rest and who required urgent revascularization because their symptoms were resistant to medical therapy were randomized to receive BC (n = 70) or crystalloid cardioplegia (CC) (n = 70). The operative mortality rate was 2.8%, the incidence of myocardial infarction was 8.6%, the incidence of low output syndrome was 18% and morbidity (myocardial infraction or low output syndrome) was 23%. Patients who received BC had a significantly lower mortality rate (BC, 0%; CC, 5%; p less than 0.05) and incidence of myocardial infarction (BC, 4%; CC, 13.5%; p less than 0.05) or low output syndrome (BC, 10%; CC, 19%; p less than 0.05). The highest postoperative CK-MB level was less after BC (BC, 31 +/- 17 U/L; CC, 56 +/- 13 U/L; p less than 0.05). Preoperative predictors of postoperative morbidity in addition to the type of cardioplegia included the response to medical therapy, persistent ischemic electrocardiographic changes, left ventricular ejection fraction, and age. A multivariate analysis identified the type of cardioplegic protection (p = 0.008) and age (p = 0.05) as significant independent predictors of postoperative morbidity. BC reduced the risk of urgent revascularization for unstable angina.

Age Factors↗

PubMed1986

Diltiazem cardioplegia. A balance of risk and benefit.

Calcium channel blockers may prevent myocardial injury during cardioplegia and reperfusion. A prospective, randomized trial was instituted to evaluate the hemodynamic and myocardial metabolic recovery in 40 patients undergoing elective aorta-coronary bypass with either diltiazem in crystalloid potassium cardioplegia (n = 20) or crystalloid potassium cardioplegia (n = 20). In a preliminary trial, doses between 150 and 250 micrograms/kg reduced the period of heart block after cross-clamp removal (90 +/- 110 minutes) from that found with higher doses and improved myocardial metabolism. In the randomized trial, diltiazem cardioplegia (150 micrograms/kg) produced coronary vasodilatation during cardioplegia and produced less reactive hyperemia during reperfusion. Myocardial oxygen extraction was lower and myocardial lactate production was less after diltiazem cardioplegia during reperfusion. Tissue adenosine triphosphate and creatine phosphate concentrations were preserved better after diltiazem cardioplegia. The postoperative creatine kinase MB levels were less (p less than 0.05) after diltiazem cardioplegia, which indicated less myocardial injury. Postoperative volume loading demonstrated that systolic function (the relation between systolic blood pressure and end-systolic volume index) was depressed after diltiazem cardioplegia compared to crystalloid cardioplegia, but cardiac index was higher because afterload (mean arterial pressure) was lower and preload (end-diastolic volume index) was higher. Diltiazem cardioplegia preserved high-energy phosphates, improved postoperative myocardial metabolism, and reduced ischemic injury after elective coronary bypass. However, diltiazem was a potent negative inotrope and produced prolonged periods of electromechanical arrest. Diltiazem cardioplegia may be of value in patients with severe ischemia but should be used with caution in patients with ventricular dysfunction, and a dose-response relation must be established at each institution before clinical use.

Benzazepines↗

PubMed1986

Accelerated myocardial metabolic recovery with terminal warm blood cardioplegia.

Although blood cardioplegia provides excellent protection, myocardial metabolic recovery is delayed. To evaluate the benefits of a terminal warm cardioplegic infusion after cold blood cardioplegia, we performed a prospective randomized trial in 20 patients undergoing elective coronary bypass grafting. Eleven patients received cold blood cardioplegia and nine patients received cold blood cardioplegia and warm blood cardioplegia before cross-clamp removal (hot shot). The hot shot provided oxygen and removed excess lactate from the arrested heart. After the hot shot lactate was extracted by the heart and tissue adenosine triphosphate and glycogen concentrations were preserved. Atrial pacing and volume loading 3 and 4 hours postoperatively decreased myocardial lactate extraction after cold blood cardioplegia but increased lactate extraction after the hot shot. Left atrial pressures were higher at similar end-diastolic volumes (by nuclear ventriculography), which suggested decreased diastolic compliance after cold blood cardioplegia. Terminal warm blood cardioplegia accelerated myocardial metabolic recovery, preserved high-energy phosphates, improved the metabolic response to postoperative hemodynamic stresses, and reduced left atrial pressures.

Adenosine Triphosphate↗

PubMed1985

A comparison of nitroglycerin and nitroprusside: I. Treatment of postoperative hypertension.

Nitroglycerin improves perfusion to ischemic myocardial regions and therefore has theoretical advantages over sodium nitroprusside to treat hypertension (mean arterial pressure [MAP] greater than 95 mm Hg) following coronary bypass operation. Thirty-three hypertensive patients were randomized to an initial infusion of either nitroglycerin or nitroprusside in a crossover trial designed to reduce MAP to 85 mm Hg. Thermodilution cardiac output measurements permitted calculation of left ventricular stroke work index (LVSWI), and nuclear ventriculograms permitted estimation of left ventricular ejection fraction, left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). Coronary sinus blood flow was measured by the continuous thermodilution technique, and arterial and coronary sinus lactate measurements permitted calculation of myocardial lactate flux (MVL). Both nitroglycerin and nitroprusside reduced MAP (-25 +/- 12 mm Hg and -20 +/- 10 mm Hg, respectively; not significant [NS]). Nitroglycerin reduced LVSWI more than did nitroprusside (-15 +/- 13 gm-m/m2 and -7 +/- 9 gm-m/m2, respectively; p less than 0.01). Both agents increased left ventricular ejection fraction (nitroglycerin, +8 +/- 8%, and nitroprusside, +10 +/- 7%; NS), and decreased LVEDVI (-20 +/- 22 ml/m2 and -11 +/- 17 ml/m2, respectively; NS) and LVESVI (-13 +/- 14 ml/m2 and -10 +/- 12 ml/m2, respectively; NS). Coronary sinus blood flow decreased with both drugs (NS), but MVL increased with nitroglycerin (+0.02 +/- 0.14 mmol/min) and decreased with nitroprusside (-0.02 +/- 0.02 mmol/min) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗

PubMed1985

A comparison of nitroglycerin and nitroprusside: II. The effects of volume loading.

The treatment of postoperative hypertension with nitroglycerin or nitroprusside reduces cardiac filling, and volume loading is required to maintain hemodynamic and metabolic stability. Postoperative hypertension (mean arterial pressure greater than 95 mm Hg) developed in 33 patients who were randomized to an initial infusion of nitroglycerin or nitroprusside in a crossover trial. Volume loading (a rapid infusion of 250 to 500 ml of colloid to raise the left atrial pressure 2 to 4 mm Hg) was instituted prior to hypertension and again following the crossover trial during the infusion of nitroglycerin (11 patients) and nitroprusside (13 patients). Volume loading increased left ventricular end-diastolic volume index (LVEDVI) as documented by nuclear ventriculography, cardiac index (CI), and left ventricular stroke work index (LVSWI). Although CI was higher (p less than 0.01) with nitroprusside at any level of LVEDVI, myocardial performance (the relation between LVSWI and LVEDVI) was not different. Diastolic compliance (the relation between left atrial pressure and LVEDVI) was increased (p less than 0.01) with nitroglycerin. Myocardial metabolism was assessed by calculating myocardial lactate flux (MVL), the product of myocardial lactate extraction and coronary sinus blood flow by the thermodilution technique. Volume loading increased MVL during nitroglycerin therapy and decreased (p less than 0.01) MVL during nitroprusside therapy. Volume loading restored preload and increased CI with both nitroglycerin and nitroprusside. Only nitroglycerin improved myocardial lactate utilization. Nitroglycerin is the preferred vasodilator when ischemia is suspected after coronary bypass operations.

Cardiac Volume↗

PubMed1985

Laboratory evaluation of patients with vascular occlusive disease.

In addition to the determination of the presenting symptom of patients with peripheral vascular occlusive disease, evaluation of these patients may include the noninvasive measurements of ankle/arm pressure ratio, limb blood flow, and treadmill testing to evaluate the severity of the reduction in blood flow. We have included metabolic studies to assess the effect of this reduced blood flow in patients with stable intermittent claudication (n = 20), and with end-stage ischemia (night and rest pain) (n = 11), and in a control group without vascular disease (n = 8). No correlations were found between the resting limb blood flow, ankle/arm pressure ratios, maximum walking distance, and stated walking distance for the patients with stable claudication. Although the oxygen consumption was reduced only in the patients with end-stage ischemia, the percent oxygen extraction was increased to the same level in the patients with stable claudication and those with end-stage ischemia. Intramuscular stores of high-energy phosphates and glycogen were maintained in all groups with the lactate/pyruvate ratio increased only in the patients with end-stage ischemia. The complex interrelationships between the rate and distribution of blood flow with exercise and enzyme adaptation in patients with vascular disease make current resting hemodynamic and metabolic evaluations a poor reflection of the severity of the clinical condition within each patient group. Therefore laboratory testing may offer no advantage over clinical presentation in the overall evaluation of these patients.

Adenosine Triphosphate↗

PubMed1985

Hemodynamic and myocardial metabolic consequences of PEEP.

The cardiac effects of positive end expiratory pressure (PEEP) were examined in 50 patients six hours after elective coronary bypass surgery. Increasing the level of PEEP from 5 to 10 to 15 cm H2O decreased cardiac index (evaluated by thermodilution), stroke index and left ventricular end diastolic volume index without a change in left ventricular ejection fraction (evaluated by nuclear ventriculography). Right ventricular end diastolic volume index remained unchanged. Coronary sinus blood flow (measured by the continuous thermodilution technique) and myocardial oxygen and lactate consumption were unchanged with the application of 15 cm H2O PEEP. In 21 patients, volume loading (250 ml [mL] of plasma) was performed at 5 cm, and again at 15 cm H2O PEEP. Volume loading produced a similar increase in cardiac volumes and cardiac index at 5 and 15 cm H2O PEEP. Right and left ventricular performance and left ventricular systolic function were not altered by PEEP (by analyses of covariance). Coronary sinus blood flow and myocardial oxygen consumption increased with volume loading at 5 and 15 cm H2O of PEEP, but myocardial lactate utilization tended to increase at 5 cm, and decrease at 15 cm H2O PEEP (p = 0.08). Of the 33 patients who underwent complete hemodynamic and metabolic measurements, 16 increased cardiac lactate utilization at 15 cm H2O PEEP and 17 decreased cardiac lactate utilization at 15 cm H2O PEEP. PEEP decreased cardiac index, perhaps by reducing left but not right ventricular volumes. Volume loading during PEEP restored cardiac index and revealed no depression in myocardial performance or systolic function. With the application of PEEP, myocardial metabolism was maintained in half the patients, but ischemic metabolism was observed in the other half.

Blood Pressure↗

PubMed1985

Myocardial metabolism and ventricular function following cold potassium cardioplegia.

Transient alterations in myocardial metabolism and ventricular function were observed after elective coronary bypass grafting despite apparently adequate intraoperative protection with cold potassium cardioplegia. Ninety patients had serial hemodynamic measurements and coronary sinus catheters inserted. Thirty-three patients had thermodilution coronary sinus flow catheters inserted to measure coronary sinus blood flow and to evaluate the myocardial utilization of oxygen and lactate. Nuclear ventriculograms were performed in 43 patients to assess ventricular function. Cardiac index fell after discontinuation of cardiopulmonary bypass and then rose between 2 and 24 hours postoperatively. Myocardial oxygen consumption steadily increased during this period. Myocardial lactate production reverted to lactate extraction 30 minutes after reperfusion. Reactive hyperemia was present during the first 10 minutes after cross-clamp release, and coronary sinus blood flow increased gradually during the first 24 hours postoperatively. The response to the stress of volume loading (the infusion of 250 to 500 ml of a colloid solution) and atrial pacing (at a rate of 110 beats/min) was evaluated 2 to 4 hours postoperatively (EARLY) and between 4 to 6 hours postoperatively (LATE). Volume loading resulted in a decrease in lactate extraction EARLY and an increase LATE (EARLY: -0.07 +/- 0.35 mmol/L; LATE: 0.08 +/- 0.32 mmol/L, mean +/- standard deviation not significant). Atrial pacing resulted in a decrease in lactate extraction EARLY and an increase LATE (EARLY: -0.11 +/- 0.34 mmol/L; LATE: 0.14 +/- 0.36 mmol/L, p less than 0.05). Diastolic compliance (the relation between the end-diastolic volume index) decreased between EARLY and LATE. Systolic function (the relation between the systolic blood pressure and the end-systolic volume index) and myocardial performance (the relation between the left ventricular stroke work index and the end-diastolic volume index) were unchanged. Ejection fraction correlated inversely with the end-diastolic volume index and did not represent an independent index of contractility. After elective coronary bypass grafting and cold crystalloid cardioplegia, myocardial metabolism recovered slowly. Hemodynamic stresses should be avoided in the early postoperative period to prevent progressive ischemic injury.

Adult↗