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S Reiz

Publications and source records attributed to S Reiz.

At least 19 recordsLinked to original sources

A comparison of the electrocardiographic cardiotoxic effects of racemic bupivacaine, levobupivacaine, and ropivacaine in anesthetized swine.

UNLABELLED: We sought, in this observer-blinded study, to determine the lethal dose for each of the local anesthetics levobupivacaine (L), racemic bupivacaine (B), and ropivacaine (R), and to compare their respective effects on the QRS interval of the precordial electrocardiograph after intracoronary injection. Anesthetized swine were instrumented with a left anterior descending artery coronary angiography catheter and injected with increasing doses of L, B, or R according to a randomized protocol. The doses administered were 0. 375, 0.75, 1.5, 3.0, and 4.0 mg, with further doses increasing in 1-mg increments until death occurred. Plotting the mean maximum QRS interval as a function of the log(10) mmol dose allowed the following cardiotoxicity potency ratios to be determined for a doubling of QRS duration-B:L:R = 2.1:1.4:1. The lethal doses in millimoles (median/range) for L and R were (0.028/0.024-0.031) and (0.032/0.013-0.032), respectively, and were significantly higher than for B (0.015/0.012-0.019) - (P < 0.05, n = 7 for all groups). The lethal dose did not differ between R and L. Thus, the cardiotoxicity potency ratios for the three anesthetics based on lethal dose were: 2.1:1.2:1. If the anesthetic potencies for B and L are similar, the latter should have less potential for cardiotoxicity in the clinical situation. IMPLICATIONS: Animal experiments have shown levobupivacaine and ropivacaine to be less cardiotoxic than racemic bupivacaine. This in vivo study, using a validated swine model, compared the relative direct cardiotoxicities of these three local anesthetics. The lethal dose did not differ between levobupivacaine and ropivacaine, but was lowest for racemic bupivacaine.

Amides↗

In vivo whole-body resting energy expenditure and insulin action in human malignant hyperthermia.

BACKGROUND: Malignant hyperthermia (MH) is a pharmacogenetic disease triggered by volatile anesthetics or succinylcholine. The disorder is heterogenetic and caused by abnormal calcium regulation within skeletal muscle cells. No clear metabolic differences have been found in MH-susceptible (MHS) persons in vivo while not having MH episodes, but some reported signs suggest that insulin action and energy turnover might be altered in muscle of MHS persons. METHODS: In fasting and insulin-stimulated conditions, using the glucose clamp technique and indirect calorimetry, we assessed in vivo resting energy expenditure (REE) and nutrient utilization rates in 10 MHS, 5 MH-equivocal (MHE) and 10 MH-negative (MHN) persons from 14 families. With a model using the persons' fat-free mass, fat mass, age, and gender, we calculated their predicted REE and compared it with measured REE in 10 MHS and 10 MHN persons (measured - predicted = residual REE). RESULTS: In vivo measured REE and glucose disposal rates were similar in 10 MHS and 10 MHN persons. Only during insulin stimulation was residual REE greater in MHS persons (6.4%; P = 0. 013). CONCLUSIONS: In vivo insulin action is unimpaired in MHS persons. Although the absolute values of whole-body REE are the same in MHS and MHN persons, the part of REE independent of the determinants fat-free mass, fat mass, age, and gender is moderately greater in MHS than in MHN persons during insulin exposure. This suggests that MH susceptibility might influence insulin-stimulated energy turnover in muscle.

Adult↗

Diaphragmatic activity after laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy is presumed to induce a reduction in diaphragmatic activity. Indirect indices of diaphragmatic function based on tidal changes in pressures and cross-section area measurements can be unreliable in the postoperative phase. The present study evaluates diaphragmatic activity by directly recording diaphragmatic EMG (EMGdia) data, along with indirect indices. METHODS: Thirteen adult patients (American Society of Anesthesiologists physical status I or II) undergoing laparoscopic cholecystectomy were examined preoperatively for inspiratory tidal changes in gastric (Pgas-insp) and esophageal (Peso-insp) pressures, and tidal changes in ribcage (Vthor) and abdominal (Vabd) cross-section areas and then again at 1, 6, and 24 h postoperatively combined with EMGdia recordings. Variations in inspiratory gastric (deltaPgas-insp) and inspiratory transdiaphragmatic (deltaPdi-insp) pressures were derived from the above. RESULTS: Laparoscopic cholecystectomy induced a significant reduction in mean deltaPgas-insp, mean deltaPdi-insp, and mean Vabd indicating a reduction of diaphragmatic activity postoperatively. DeltaPdi-insp decreased from 11.8+/-4.0 cm H2O preoperatively to 5.7+/-5.7 cm H2O at 1 h and 6.6+/-5.1 cm H2O at 6 h postoperatively (mean +/- SD; P < 0.05). Vabd decreased from 327.0+/-113.0 ml preoperatively to 174.0+/-65.0 ml at 1 h and 175.0+/-98.0 ml at 6 h postoperatively (mean +/- SD; P < 0.05). These values had partially recovered at 24 h. CONCLUSION: The direct and indirect indices of diaphragmatic activity taken together confirm the presence of reduction in diaphragmatic activity after laparoscopic cholecystectomy followed by its partial recovery at 24 h.

Adult↗

Circulatory effects of volatile anesthetic agents.

Modern general anesthesia includes the use of multimodal techniques, mixing volatile or intravenous agents with opioids and/or regional anesthesia. Therefore, most circulatory side effects of inhaled agents are seldom observed. They all produce dose-dependent decrease of systolic and diastolic function and depress baroreflexes to a varying degree. Desflurane, and to a much lesser degree, isoflurane, may cause sympathetic nervous system activation when inhaled concentration is rapidly increased to above 1.5 MAC. This appears to be the result of central activation rather than airway irritation. The older volatile anesthetics halothane and enflurane have no or minimal effect on coronary vascular tone. In contrast, the more recent agents all limit coronary vasodilator reserve by direct effect upon coronary resistance vessels, sevoflurane less than isoflurane and desflurane at equipotent anesthetic dose. Although isoflurane and desflurane appear to produce myocardial ischemia by non-hemodynamically related mechanisms more frequently than halothane or fentanyl in patients at risk, no particular agent has been identified to carry greater risk for adverse cardiac outcome than others.

Anesthetics, Inhalation↗

A new method of using gas exchange measurements for the noninvasive determination of cardiac output: clinical experiences in adults following cardiac surgery.

New mathematical algorithms have been applied to a computer controlled closed breathing circuit system for non-invasive measurement of cardiac output (COniv). This system has been described in an animal study. Forty patients were studied 5 and 18 hours after cardiac surgery using the thermodilution technique as the reference (COtd). The variables entered into the algorithms for COniv were oxygen uptake, carbon dioxide elimination, end-tidal carbon dioxide partial pressure, tidal volume and arterial oxygen saturation. Mixed venous carbon dioxide partial pressure was obtained from an automatically implemented short rebreathing manoeuvre. Pulmonary perfusion was calculated by a modified Fick equation for carbon dioxide and the shunt flow added to obtain COniv. During mechanical ventilation, there was a good agreement between COtd and COniv (r = 0.8). The bias was -0.14 l/min and the precision was 0.77 l/min. The reproducibility of COniv was 0.03 l/min and for COtd -0.03 l/min with a standard deviation of the difference being 0.35 l/min for COniv and 0.31 l/min for COtd. In awake, but sedated extubated patients, the method proved unsatisfactory on account for uneven tidal volumes and difficulties with leakage around the mouth piece. We conclude that this new technique provides reliable and reproducible measures of cardiac output in sedated, ventilated patients.

Adult↗

Anaesthesia for abdominal vascular surgery in patients with coronary artery disease (CAD), Part I: Isoflurane produces dose-dependent coronary vasodilation.

The effects of anaesthesia for major abdominal vascular surgery on coronary flow regulation and mechanisms of myocardial ischaemia were studied in 56 patients with CAD, using a randomized, partly double-blinded protocol. After induction with fentanyl (3 micrograms.kg-1) and thiopentone (2-4 mg.kg-1) and tracheal intubation, principal anaesthetics were nitrous oxide/oxygen (60/40) with isoflurane (n = 20), halothane (n = 19) or fentanyl (15-20 micrograms.kg-1) (n = 17). Conventional invasive techniques and coronary venous retrograde thermodilution were used to assess systemic and coronary haemodynamics. Coronary vascular resistance was estimated from myocardial oxygen extraction. Myocardial ischaemia was diagnosed by 12-lead ECG and/or anterior wall motion abnormalities by cardiokymography and/or myocardial lactate production. When adjustment of anaesthetic dose was insufficient for haemodynamic control, i.v. phenylephrine and nitroglycerine were administered to treat hypotension and hypertension or cardiac failure respectively. Measurements were performed at four specific intervals; awake, before surgery and 10 and 30 min after abdominal incision. Comparable changes of systemic haemodynamics and myocardial oxygen consumption were observed in the three groups. Coronary vasodilation was evidenced in isoflurane patients only and was linearly dose-dependent (P < 0.001). Partial Least Squares Projections to Latent Structures modelling with cross validation confirmed this dose-dependency and ruled out a clinically measurable influence by intervention drugs or simultaneous systemic haemodynamic abnormalities. The incidence of myocardial ischaemia during anaesthesia and surgery was comparable in the three groups (35, 37 and 24%, respectively) and there was an association with systemic haemodynamic aberrations in 19 of the 27 ischaemic episodes. In contrast to ischaemic halothane and fentanyl patients, isoflurane patients with ischaemia had significantly lower myocardial oxygen extraction (P = 0.008 and P = 0.001, respectively), indicating that the oxygen extraction reserve was not utilized in a normal way during ischaemia.

Abdomen↗

Anaesthesia for abdominal aortic surgery in patients with coronary artery disease, Part II: Effects of nitrous oxide on systemic and coronary haemodynamics, regional ventricular function and incidence of myocardial ischaemia.

This study examines the effects of nitrous oxide on haemodynamics, anterior left ventricular (LV) function and incidence of myocardial ischaemia in abdominal vascular surgical patients with coronary artery disease. Forty-seven patients were randomly assigned to isoflurane-fentanyl anaesthesia with nitrous oxide-oxygen vs air-oxygen (control). Systemic and coronary haemodynamics, 12-lead ECG, LV anterior wall motion by cardiokymography (CKG) and myocardial lactate balance were recorded at four intervals: before and during anaesthesia and 10 and 30 minutes into surgery. Systemic haemodynamics were controlled by anaesthetic dose, and, when insufficient, by i.v. nitroglycerine (NG) in case of LV failure (PCWP > 18 mmHg) and by phenylephrine during hypotension. We found that nitrous oxide was associated with greater need for i.v. nitroglycerin (patients: P = 0.031, episodes P = 0.005) and more myocardial ischaemia (patients P = 0.012, episodes P = 0.001) despite systemic and coronary haemodynamics comparable to the control group. We conclude that nitrous oxide, known to have both sympathomimetic and cardiodepressive actions, produced cardiodepression in the face of sympathetic stimulation. Our study design did not allow to conclude if myocardial ischaemia was the consequence of increased wall stress or a reason for the observed LV dysfunction. The higher incidence of introperative myocardial ischaemia and need for NG did not cause increased cardiac morbidity.

Abdomen↗

On-line computerized vectorcardiography monitoring of myocardial ischemia during coronary angioplasty: comparison with 12-lead electrocardiography.

BACKGROUND: With new interventions minimizing ischemic myocardial injury, accurate and reliable techniques for the detection and continuous monitoring of myocardial ischemia are essential. We compared two techniques used for the detection of myocardial ischemia during coronary angioplasty: on-line computerized vectorcardiographic (cVCG) monitoring and the standard electrocardiography (ECG) leads or the complete 12-lead ECG. METHODS: Thirty patients scheduled for routine angioplasty were included in the study. cVCG was recorded continuously. The electrodes were placed according to the lead system described by Frank and connected to a computerized system for on-line vectorcardiography. A 12-lead ECG was recorded simultaneously. The absolute variable spatial ST vector magnitude (ST-VM) and the relative variable spatial ST change vector magnitude (STC-VM) were calculated and compared with the standard 12-lead ECG for the detection of ischemia. RESULTS: The sum of deviation in ST segment in all 12 standard ECG leads correlated closely with STC-VM, irrespective of which artery was occluded. STC-VM indicated ischemia during the first balloon inflation in 87% of the patients and demonstrated ischemia in more patients than the standard 12-lead ECG. Myocardial ischemia was not demonstrated by ST-VM in five out of 26 patients with ischemia according to STC-VM. In these cases, mainly directional vector changes and fewer changes in magnitude were observed. CONCLUSION: Compared with 12-lead ECG, on-line cVCG is a more sensitive method of detecting myocardial ischemia during coronary angioplasty and the reading is easier and faster. Our results support STC-VM > or = 0.050 mV as the criterion for ischemia during angioplasty; ST-VM should be applied together with STC-VM.

Angina Pectoris↗

Quantification of myocardium at risk and detection of reperfusion by dynamic vectorcardiographic ST segment monitoring in a pig occlusion-reperfusion model.

OBJECTIVE: The aim was to investigate whether continuous computerized vectorcardiographic monitoring of absolute spatial ST vector magnitude (ST-VM) and spatial ST change vector magnitude (STC-VM) during coronary occlusion could be used to estimate the size of myocardium at risk; and also to test whether reperfusion could be distinguished from sustained occlusion by continuous monitoring of ST vector alterations. METHODS: Computerised vectorcardiographic monitoring via Frank leads was applied in a closed chest occlusion-reperfusion pig model. Coronary occlusion over 24 h was produced in 20 animals by injecting a 2 mm ball into the left anterior descending coronary artery (n = 7), the right coronary artery (n = 8), and the left circumflex coronary artery (n = 5). Another 31 pigs were reperfused by retraction of the ball after 30 (n = 10), 60 (n = 15), or 90 (n = 6) min of left anterior descending artery occlusion. The extent of the myocardium at risk was measured by autoradiography. RESULTS: Seven animals were excluded. Irrespective of occluded coronary artery the relative parameters STC-VM over the first 30 min of occlusion correlated closely with area at risk, that is, the mean STC-VM between 10 and 30 min of occlusion (r = 0.78 p < 0.001). The absolute parameter ST vector magnitude (ST-VM) did not reflect ischaemia in 16/44 animals and did not correlate significantly with area at risk. The weight of myocardium at risk (MAR) was predictable from STC-VM: MAR weight (measured) = 0.97 x MAR weight (predicted) + 0.26 (g), r = 0.81, p < 0.001. STC-VM decline rate, time to STC-VM plateau, and cumulated sum plots of STC-VM were all able to distinguish reliably between reperfused animals and those with permanent occlusion. A paradoxical increase in STC-VM - "reperfusion peak" - was detected in 17/31 (55%) of the animals. This phenomenon was related to large amount of myocardium at risk or to a long occlusion time. CONCLUSION: Dynamic vectorcardiographic ST monitoring provides adequate estimation of myocardium at risk and enables detection of reperfusion in experimental myocardial ischaemia.

Animals↗

Ischaemia and reperfusion induced transient QRS vector changes: relationship to size of the ischaemic territory.

OBJECTIVE: The aim was to investigate QRS vector changes during the first 30 min of coronary occlusion or the early phase of reperfusion with special reference to location and size of myocardium at risk. METHODS: 24 h experiments were performed in closed chest anaesthetised pigs. QRS vectors were studied by computerised vectorcardiography via Frank leads. Occlusion of the left anterior descending coronary artery followed by reperfusion was induced in 23 pigs and a sustained occlusion in 20 pigs: left anterior descending coronary artery in seven, right coronary artery in eight, and left circumflex coronary artery in five. Myocardium at risk was measured in postmortem autoradiograms. Eight animals were excluded. RESULTS: Four minutes after occlusion, QRS(mean) deviated towards the ischaemic region in 34/35 animals and returned thereafter at varying speeds. In half of the reperfused animals, deviation of QRS vectors towards the ischaemic territory was also observed during the first minutes of reperfusion. A paradoxical increase in QRS vector changes, "reperfusion peak", was recorded during the initial minutes of reperfusion in 12/19 animals. Maximum spatial QRS vector magnitude increased in all right coronary or left circumflex coronary occlusion animals compared to 6/25 in left anterior descending coronary occlusion animals. QRS vector difference, change in spatial QRS vector angle, and maximum change in QRS azimuth 4 min after occlusion correlated significantly with extent of myocardium at risk. CONCLUSIONS: Marked directional and quantitative QRS vector changes, with significant relation to size and location of myocardium at risk, were recorded during the initial minutes of ischaemia. The transient increase in QRS vector changes during the first minutes of reperfusion deserves further exploration as a new indicator of reperfusion.

Animals↗

Enzyme and immunohistochemical assessment of myocardial damage after ischaemia and reperfusion in a closed-chest pig model.

The usefulness of different enzyme and immunohistochemical stains to distinguish reversible and irreversible myocardial cell injury after experimental coronary artery occlusion of varying duration and reperfusion with or without superoxide dismutase as adjunct was investigated. Biopsies or parts of the infarcted and non-infarcted area were rapidly frozen and sectioned in series for enzyme and immunohistochemical evaluation. Sections were stained for the demonstration of phosphorylase, myofibrillar ATPase and mitochondrial oxidative enzymes and also with periodic acid-Schiff, alizarin red S and routine histological stains. Other sections in series were stained with antibodies against fibronectin and the intermediate filament proteins desmin and vimentin. In 49 biopsies a blind quantitative estimation of the area stained for fibronectin, phosphorylase and alizarin red S was performed and evaluated statistically. Phosphorylase, periodic acid-Schiff, fibronectin and alizarin red S allowed delineation of affected myocardium after 30 min of ischaemia followed by reperfusion whereas with the other stains, affected myocardium was readily detectable only after 60 or 90 min of ischaemia followed by reperfusion as well as after 24 h of ischaemia without reperfusion. The immunostaining for fibronectin was very distinct and inversely related to the phosphorylase activity. We show that fibronectin is an excellent marker for damaged cells and that these positively stained myocytes are necrotic as confirmed ultrastructurally. Using alizarin red S as a marker of calcium accumulation in myocytes, a marked discrepancy was observed between the area of fibronectin-containing myocytes and that of myocytes stained by alizarin red S. Calcium accumulation in mitochondria is thus not a prerequisite for myocyte necrosis but does occur only in some of the irreversibly damaged cells. Of special interest is the finding that there was a significant reduction of intracellular calcium in pigs where superoxide dismutase had been used as an adjunct at reperfusion, thus supporting the theory that free radicals do play a role during reperfusion of ischaemic myocardium.

Adenosine Triphosphatases↗

Transesophageal echocardiographic assessment of left ventricular function in response to labetalol for control of postoperative hypertension.

Although labetalol (LAB), the combination of an alpha- and beta-adrenergic blocking agent, is thought to be effective and safe for the control of postoperative hypertension, no study has focused on changes in left ventricular (LV) function when this drug was used to control postoperative hypertension. Therefore, this study determined the effects of LAB on hemodynamics and LV function assessed by 2D transesophageal echocardiography (TEE) in 17 patients undergoing abdominal aortic surgery who experienced a postoperative hypertensive episode. Postoperatively, patients were transferred while still intubated and under fentanyl sedation to the postanesthesia care unit where a TEE probe was inserted to provide a short-axis view of the LV. When their systolic blood pressure increased above 165 mmHg for more than 4 minutes, LAB was given in a dose of 0.75 mg/kg IV, over 2 minutes. If the blood pressure was not lowered to within 10% of the preoperative values, additional doses of LAB were given. Control of hypertension was obtained in all patients and was associated with a significant decrease in heart rate (90 +/- 19 to 70 + 13 bpm), cardiac index (4.52 +/- 1.65 to 3.36 +/- 1.55 L/min/m2), and mixed venous oxygen saturation (73 +/- 10 to 63 +/- 10%). With the lower blood pressure, end-diastolic area increased, indicating myocardial depression. In conclusion, LAB can be used to effectively control hypertension during the early postoperative period after abdominal aortic surgery. However, the reduction of blood pressure is achieved principally by the negative inotropic effect of LAB, which predominates over its vasodilator action.

Adult↗

Effects of reperfusion and superoxide dismutase on myocardial infarct size in a closed chest pig model.

OBJECTIVE: The aim was to study the effects on myocardial infarct size of reperfusion alone or of CuZn superoxide dismutase (SOD) as an adjunct to reperfusion. METHODS: Occlusion was induced in closed chest, pentobarbitone anaesthetised, mechanically ventilated pigs by injection of a 2 mm ball into a preselected coronary artery. Reperfusion was achieved by retraction of the ball via an attached filament. Twenty nine placebo treated and 25 SOD treated animals were subjected to 30 (n = 21), 60 (n = 21), and 90 (n = 12) min of coronary occlusion followed by reperfusion to 24 h; a control group of 24 pigs was subjected to a sustained occlusion for 24 h. Infarct size was assessed by tetrazolium staining and plasma creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LD). In the CuZn SOD group, 200 mg bovine CuZn SOD was given as a bolus intravenously immediately before reperfusion followed by a continuous infusion (100 mg) for 60 min. The size of the ischaemic myocardium at risk was measured from post mortem autoradiograms. RESULTS: Infarct size as percent of myocardium at risk was 46.0(SD 15.5)%, 80.1(9.9)%, and 88.9(5.0)% respectively in placebo animals with 30, 60, and 90 min occlusion, and 94.2(5.1)% in pigs with 24 h sustained occlusion. Compared to 24 h sustained occlusion, limitation of infarct size by reperfusion was only demonstrated in the 30 (p less than 0.001) and 60 min groups (p less than 0.001). Plasma values of CK, ASAT, and LD at 90 min post-reperfusion correlated closely with infarct size as assessed by tetrazolium staining and were related to occlusion duration. No myocardial salvage, as assessed by plasma ASAT, CK, or LD, was shown in the SOD treated groups. CONCLUSIONS: Early reperfusion resulted in myocardial salvage as assessed by tetrazolium staining and peak ASAT, CK, and LD at 90 min after the reperfusion. No limitation of infarct size by SOD could be demonstrated from analyses of plasma CK, ASAT, or LD.

Animals↗

A closed-chest myocardial occlusion-reperfusion model in the pig: techniques, morbidity and mortality.

Extensive preparative surgery and lengthy experimentation may lead to high rate of complications and mortality in myocardial ischaemia studies. These problems are particularly common when pigs are used as the subject as they are prone to develop lethal ventricular arrhythmias. Here, a closed-chest model is presented, in which the trauma of major preparative surgery is avoided. One-hundred and twelve pentobarbital-anaesthetized, mechanically ventilated pigs were used. Coronary occlusion was produced by injection of a 2 mm diameter ball via a modified coronary angiography catheter. Reperfusion was induced by retraction of the ball via a thin filament attached to the ball. The amount of the myocardium at risk (MAR) was 8.23 +/- 2.41% (mean +/- SD) of the left plus right ventricular weight. It was possible to carry out scheduled 24 h experiments in 87 out of 93 animals (93.5%). Preparative mortality was 1.8% and 24 h mortality 6.5%. Ventricular fibrillation (VF) occurred during preparation in 3.6%, during coronary occlusion in 7.3% and during reperfusion in 5.0% of the animals. VF was significantly related to a large zone of MAR and insufficient premedication. Catheter- or ball-induced complications were found in 10.7%. Mortality and incidence of VF are considerably lower in this closed-chest model than in a previously reported open-chest pig preparation.

Animals↗

A geriatric-anesthesiologic program to reduce acute confusional states in elderly patients treated for femoral neck fractures.

The aim of this study was to evaluate the effect of a geriatric-anesthesiologic intervention program for the prevention and treatment of acute confusional states (ACS) in elderly patients treated for femoral neck fractures. The intervention program was based on the results of previous prospective studies in similar patient populations. The outcome of the intervention, comprising 103 patients, was compared with that of an earlier study comprising 111 patients. The intervention program consisted of pre- and post-operative geriatric assessments, oxygen therapy, early surgery, prevention and treatment of peri-operative blood pressure falls and treatment of post-operative complications. The incidence of ACS was lower, 47.6%, in the intervention study compared with 61.3% (P less than 0.05) in the control study. Furthermore, the ACS that occurred in the intervention study was less severe and of shorter duration than that in the control study. The incidence of post-operative decubital ulcers, severe falls, and urinary retention was also lower. The mean duration of orthopedic ward stay was 17.4 days in the control study and 11.6 days in the intervention study (P less than 0.001). It can be concluded that the intervention program reduced the incidence, severity, and duration of ACS which resulted in a shortened orthopedic ward stay.

Aged↗

Limitation of myocardial infarct size by superoxide dismutase as an adjunct to reperfusion after different durations of coronary occlusion in the pig.

Superoxide dismutase (SOD) has been documented to limit myocardial infarct size in the richly collateralized dog heart. This study was designed to explore this concept in a low-collateralized animal model. A blind, randomized, placebo-controlled protocol was used in 65 pentobarbital-anesthetized pigs subjected to closed-chest left anterior descending coronary artery occlusion for 30 (n = 22), 60 (n = 22), and 90 (n = 14) minutes followed by reperfusion up to 24 hours from the start of occlusion. Another seven control pigs were subjected to 24 hours of permanent occlusion. A total dose of 9 mg/kg bovine CuZn SOD was administered as a bolus injection immediately before reperfusion followed by a 1-hour infusion. Infarct size was assessed by tetrazolium staining. Myocardium at risk and collateral flow were determined by using cerium-141-labeled microspheres (15 microns) during the occlusion. After 30 minutes of occlusion, infarct sizes in placebo versus SOD-treated animals were 45.5 +/- 15.7% vs. 23.8 +/- 15.6% of myocardium at risk (p = 0.007). The corresponding values after 60 minutes of occlusion were 78.6 +/- 9.3% vs. 66.9 +/- 14.6% (p = 0.035). SOD administered after 90 minutes of occlusion did not limit infarct size (88.5 +/- 4.8% vs. 92.3 +/- 5.2%). Twenty-four hours of coronary occlusion resulted in infarction of 92.4 +/- 4.2% of myocardium at risk. (All values are mean +/- SD.) Ventricular fibrillation occurred in only nine pigs distributed equally between SOD and placebo. The results indicate that CuZn SOD has the potential to further improve the myocardial salvage established by reperfusion of an ischemic pig heart territory. However, the narrow time window for limiting infarct size in the pig by reperfusion is not much extended by SOD.

Animals↗