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Biomedical subjects

K A Reimer

Publications and source records attributed to K A Reimer.

At least 91 records · Page 5Linked to original sources
PubMed1985

Right ventricular infarction with shock but without significant left ventricular infarction: a new clinical syndrome.

Right ventricular infarction has been described as concurrent with infarction involving the inferior (posterior) aspect of the left ventricular free wall and adjacent interventricular septum. Patients with right ventricular infarction typically show the ECG changes of inferior infarction in leads II, III, and aVF. This report describes two patients with right ventricular infarction but without changes in the QRS complex of the ECG, indicating an inferior infarct of the left ventricle. An autopsy-proven infarct of the right ventricular free wall with neither QRS nor other clinical evidence of left ventricular involvement was responsible for cardiogenic shock and death in one patient. This observation led to a review of a computerized data bank containing records of patients who had undergone cardiac catheterization to determine if there were other patients with clinical criteria suggesting right ventricular infarction without QRS changes of left ventricular infarction. One of the 167 patients with a history of a myocardial infarction also met the following clinical criteria: (1) transiently elevated total creatine kinase and creatine kinase myocardial band; (2) diffuse ST segment elevation without QRS changes indicative of left ventricular infarction on the ECG; (3) normal left ventricular function; (4) hemodynamic evidence of right ventricular dysfunction; and (5) cardiogenic shock.

Aged↗
PubMed1985

Failure of the xanthine oxidase inhibitor allopurinol to limit infarct size after ischemia and reperfusion in dogs.

During the acute phase of myocardial ischemia, adenine nucleotides are degraded to nucleosides and bases, especially inosine and hypoxanthine. Simultaneously, xanthine dehydrogenase is converted to xanthine oxidase, an enzyme that converts hypoxanthine to xanthine, and xanthine to uric acid, producing a superoxide anion for each molecule of hypoxanthine or xanthine oxidized. To determine if free radicals via this enzymatic source contribute to cell death in myocardial ischemia, we determined whether allopurinol, an inhibitor of xanthine oxidase, could limit infarct size in a reperfusion preparation of myocardial infarction. The circumflex coronary artery of each of 34 dogs was occluded for 40 min, followed by reperfusion for 4 days. Infarct size then was measured by histologic methods and was related to major baseline predictors of infarct size, including anatomic area at risk and collateral blood flow. Infarct size was larger (NS) in the allopurinol (n = 8) than in the control (n = 11) group, a trend that was related to slightly higher (NS) collateral blood flow in the control group. We conclude that allopurinol has no beneficial effect in this preparation of experimental myocardial infarction. The results oppose the hypothesis that free radicals, produced via the xanthine oxidase reaction, are an important contributing factor in myocardial ischemic cell death.

Allopurinol↗
PubMed1985

Effect of reperfusion late in the phase of reversible ischemic injury. Changes in cell volume, electrolytes, metabolites, and ultrastructure.

The acute effects of reperfusion on myocardium reversibly damaged by 15 minutes of severe ischemia in vivo, were studied. Changes in the adenine nucleotide pool, cell volume regulation, myocardial calcium, and ultrastructure were studied at the end of 15 minutes of ischemia and after 0.5, 3.0, and 20 minutes of reflow. Before reperfusion, adenosine triphosphate and the adenylate pool decreased by 63% and 44% of control, respectively, and the adenylate charge was reduced to 0.65. After 3 minutes of reperfusion, the adenylate charge was restored to control by the rephosphorylation of adenosine mono- and diphosphate, but adenosine triphosphate was still reduced by 45%. Mild tissue edema was detected after 0.5 minute of reflow and persisted throughout 20 minutes of reperfusion. The increased tissue water was accompanied by a slight increase in sodium and a marked increase in tissue potassium. Although massive calcium accumulation develops when irreversibly injured tissue is reperfused, no calcium overload was detected during early reperfusion of reversibly injured myocytes. Reperfusion for 3 minutes exaggerated the mitochondrial swelling induced by 15 minutes of ischemia but after 20 minutes of reperfusion, myocardial ultrastructure was essentially normal except for rare swollen, or disrupted, mitochondria. Thus, the cellular abnormalities associated with brief periods of ischemia persist for variable periods of time after reperfusion of reversibly injured myocytes. First: although adenine nucleotide repletion occurs very slowly, the adenylate charge was restored after 3 minutes, indicating rapid resumption of mitochondrial adenosine triphosphate production. Second: calcium overload was not detected, but myocardial edema and increased potassium persisted throughout the 20 minutes of reperfusion. Third: the ultrastructural consequences of ischemia were nearly reversed after 20 minutes of reperfusion.

Adenine Nucleotides↗
PubMed1985

Animal models for protecting ischemic myocardium: results of the NHLBI Cooperative Study. Comparison of unconscious and conscious dog models.

The Animal Models for Protecting Ischemic Myocardium Study was undertaken for the purpose of developing reproducible animal models that could be used to assess interventions designed to limit infarct size. This paper describes the results obtained in an unconscious dog model and in a conscious dog model, developed in three participating laboratories. The unconscious dog model, involving reperfusion after 3 hours of ischemia in open-chest dogs, was intended to determine whether therapy followed by early reperfusion would limit infarct size more than reperfusion alone. The conscious dog model used chronically instrumented dogs and permanent coronary occlusion to better mimic myocardial infarction in man. In both models, the proximal circumflex artery was occluded, and the primary experimental endpoint was infarct size, as measured by histological techniques 3 days after the initial occlusion. Infarct size was analyzed in relation to baseline variables including the anatomic area at risk, collateral blood flow to the subepicardial zone of ischemia and hemodynamic determinants of myocardial metabolic demand. Most of the variation in infarct size in control dogs could be related to variation in the area at risk, collateral blood flow, and rate pressure product. Using multivariate analysis and groups of 15 dogs, an intervention that limited infarct size by 10-13% of the area at risk would have been detected 50% of the time. Larger treatment effects would be detected more readily, and smaller effects often would be missed, unless group sizes were larger. Two drugs, verapamil and ibuprofen, were evaluated in both models, with experimental group sizes averaging 13 and 20 dogs, in the unconscious and conscious models, respectively. Three of 15 verapamil-treated dogs in the unconscious model study had much smaller infarcts than expected from baseline parameters. With these exceptions, neither drug limited infarct size in either model.

Anesthesia↗
PubMed1984

Comparison of enzymatic and anatomic estimates of myocardial infarct size in man.

Enzymatic estimates of myocardial infarct size based on plasma levels of MB creatine kinase (MB-CK) were compared with anatomic infarct size in 49 human hearts obtained at autopsy. The patients studied had been enrolled in the Multicenter Investigation of Limitation of Infarct Size (MILIS) study program within 18 hr of the onset of acute infarction and were treated at one of five participating hospitals. Infarct size was estimated from serial measurements of plasma MB-CK made at the core laboratory for CK analysis. Hearts obtained at autopsy were studied independently by the core pathology laboratory without knowledge of the MB-CK levels or clinical results. Data from the two laboratories were compared at the data coordinating center. Of 49 hearts, 12 were excluded either because anatomic infarct size could not be established or because the infarct occurring at the time of enrollment in the MILIS study could not be distinguished with certainty from other infarcts. Of the remaining 37 hearts, peak MB-CK level was available in 36, but samples sufficient for estimation of infarct size were available in only 25. The overall correlation coefficient (Spearman) was .87 for these 25 hearts, indicating that enzymatic estimates of infarct size correlate closely with anatomic measurements. The results indicate that CK estimates of myocardial infarct size represent a valid clinical end point for assessing myocardial infarct size, and the effect of therapy thereon, in groups of treated and control patients.

Autopsy↗
PubMed1984

Verapamil in two reperfusion models of myocardial infarction. Temporary protection of severely ischemic myocardium without limitation of ultimate infarct size.

The ability of verapamil to protect severely ischemic myocardium was assessed in dogs using 40 minutes of temporary coronary occlusion. Reperfusion was established for 4 days after which infarcts were sized histologically. Untreated dogs developed subendocardial infarcts (the more moderately ischemic subepicardial region being salvaged by reperfusion). Pretreatment with verapamil reduced the size of these subendocardial infarcts from 34 +/- 8 to 8 +/- 3% of the ischemic circumflex vascular bed at risk (identified by postmortem perfusion of the previously occluded and unoccluded arteries with different dyes). Thus, verapamil prevented cell death in the severely ischemic subendocardial region for the 40-minute test period. In a second study to establish whether verapamil could delay cell death for a longer period of time in the less severely ischemic subepicardial region, a 3-hour period of coronary occlusion was used. This period of occlusion caused infarcts averaging 60 +/- 6% of the ischemic area at risk in untreated dogs. Dogs treated with verapamil 15 minutes postocclusion and throughout the remaining 165 minutes of the 3-hour test period had no limitation of infarct size (53 +/- 3% of the area at risk). In this 3-hour study, the effect of variation in collateral blood flow on infarct size was evaluated by plotting infarct size versus subepicardial collateral flow. Verapamil neither improved collateral flow nor altered the relationship between infarct size and baseline collateral flow. Thus, pretreatment with verapamil prevented necrosis of severely ischemic myocytes, when reperfusion was established at 40 minutes, but failed to prevent necrosis of moderately ischemic myocardium and thus failed to limit infarct size when the period of coronary occlusion was prolonged to 3 hours and treatment was started 15 minutes after the onset of ischemia.

Animals↗
PubMed1983

Pathobiology of acute myocardial ischemia: metabolic, functional and ultrastructural studies.

Acute myocardial ischemia induced by coronary occlusion in dogs is most severe in the subendocardial region, whereas more collateral blood flow is often present in the subepicardial region. Initially, all ischemic myocytes are reversibly injured, but beginning at 15 to 20 minutes after the onset, and continuing for 3 to 6 hours, there is a wave front of cell death from the subendocardial region to the less ischemic subepicardial region, such that by 6 hours, the final transmural extent of the infarct is established. Thus, ischemic myocardium cannot be salvaged by reperfusion after greater than or equal to 6 hours of coronary occlusion in open-chest anesthetized dogs. In the severely ischemic subendocardial region, most of the creatine phosphate is lost within the first 3 minutes of ischemia in vivo, and adenosine triphosphate (ATP) is depleted to 35% of control by 15 minutes (when cellular injury is still reversible), and to less than 10% of control at 40 minutes (when injury is irreversible). Tissue ATP content and other indexes of subcellular damage have also been compared after different periods of ischemia using a model of total myocardial ischemia in vitro. As long as the ATP of the tissue was not depleted below 5 mumols/g dry weight, incubated slices of injured myocardium resynthesized high-energy phosphates and excluded inulin. However, lower tissue ATP was associated with depressed high-energy phosphate resynthesis and failure of cell volume regulation. Overt membrane damage, as measured by an increased inulin-diffusible space, was detected only after the tissue ATP decreased to less than 2.0 mumols/g of dry weight. Thus, marked ATP depletion is associated with the onset of structural and functional indexes of irreversible injury. However, whether irreversibility is caused by the marked ATP depletion or by other concomitant metabolic consequences of ischemia is not known. Myocardial ischemic cellular injury is reversible despite depletion of 70% of the control ATP. Nevertheless, when myocyte injury is reversible, there is slow repletion of adenine nucleotides. This slow metabolic recovery may explain the delayed recovery of contractile function observed after reperfusion of ischemic myocardium.

Adenine Nucleotides↗
PubMed1983

High energy phosphates, anaerobic glycolysis and irreversibility in ischemia.

The effects of severe regional myocardial ischemia in vivo and total ischemia in vitro on energy production by anaerobic glycolysis in dogs are described. The critical feature of ischemic injury in terms of the adenine nucleotide pool is the fact that the demand of severely or totally ischemic tissue for HEP exceeds the capacity of the damaged myocytes to produce it. The consequent depletion of ATP to very low levels and the destruction of the adenine nucleotide pool are associated with, or may be casually related to, the loss of cellular viability.

Adenine Nucleotides↗
PubMed1983

Prolonged depletion of ATP because of delayed repletion of the adenine nucleotide pool following reversible myocardial ischemic injury in dogs.

Sixty-five percent of the ATP and 50% of the total adenine nucleotide (sigma Ad) pool is lost from the subendocardial myocardium after 15 min of severe ischemia induced by circumflex artery occlusion in open-chest dogs (12). In the present experiment, we assessed the effects of various periods of arterial reflow following 15 min of ischemic injury on resynthesis of ATP and sigma Ad. The circumflex artery was occluded for 15 min and reperfused for 20 or 60 min or 24 or 96 hr. The mean ATP after 15 min of ischemia was reduced 62% from 5.42 +/- 0.33 to 2.08 +/- 0.21 mumol/g; and the total nucleotide content was reduced by 50%. ATP content recovered slightly during the first 20 min of reperfusion but remained markedly depressed for at least 24 hr because of the initial depletion of adenine nucleotides and because minimal salvage of de novo repletion occurred in the injured muscle during this time period. By 4 days, ATP and total adenine nucleotides were still slightly depressed but had recovered to 88% and 91% of control. Electrolyte changes and an increased inulin-diffusible space, which are characteristic of irreversibly injured myocardium, reperfused for 20 or 60 min, were not observed. Also, tissue necrosis was absent in the hearts reperfused for 24 or 96 hr. These observations indicate that the marked depression of ATP and adenine nucleotides and the slow recovery of these metabolites occurred in myocardium that nevertheless was reversibly injured in terms of cellular viability.

Adenine Nucleotides↗
PubMed1983

Evaluation of a QRS scoring system for estimating myocardial infarct size. III. Correlation with quantitative anatomic findings for inferior infarcts.

This study evaluated by quantitative autopsy correlation a previously developed scoring system for estimating the size of myocardial infarcts based on the QRS complex of the electrocardiogram. This system was tested using electrocardiograms from patients with infarcts shown by autopsy to predominate in the inferior third of the left ventricle. The study was limited to patients whose electrocardiogram did not indicate left or right ventricular hypertrophy, left or right bundle branch block, or left anterior or posterior fascicular block. Thirty-one patients from 6 medical centers met these criteria. In the electrocardiogram of 28 of the 31 patients (90%), lead a VF exhibited a Q wave of at least 30 ms. The correlation coefficient between the total QRS score and the percent infarction of the left ventricle was 0.74. In patients without confounding factors in the electrocardiogram and with single infarcts, the electrocardiogram provides a marker for infarcts in the inferior third of the left ventricle and a quantitative QRS scoring system provides an estimate of infarct size.

Aged↗
PubMed1983

Comparison of the effect of ischaemia and anoxia on the sarcolemma of the dog heart.

Contraction-band necrosis, a striking morphologic lesion, is common to many types of myocardial injury including the calcium paradox and ischaemic injury with reperfusion. This lesion is characterized by explosive swelling, massive calcium overload, and severe disruption of the myofibrils due to the formation of contraction bands. The studies reviewed in this paper provide evidence that in ischaemia and reperfusion, these changes are preceded by sarcolemmal injury that occurs during the period of ischaemia. Sarcolemmal injury was evaluated by electron microscopy and by measurements of inulin diffusible space (IDS) in thin slices of myocardium incubated in vitro. Reversibly injured ischaemic myocytes have ultrastructurally intact plasma membranes which are impermeable to inulin. Longer durations of ischaemia, sufficient to produce contraction-band necrosis during reperfusion, result in fragmentation of plasma membranes during the ischaemic intervals, and the IDS is markedly increased during subsequent incubation. Thus ultrastructural evidence of membrane damage is present early in ischaemia and is associated temporally with the increased IDS. The role of anoxia, per se, in inducing membrane damage was investigated in tissue slices incubated at 37 degrees C in crystalloidal media gassed with nitrogen. Anoxic slices produced lactate and lost ATP and adenine nucleotides, but cell volume and the IDS were not significantly increased for at least five hours (twice the time required for severe membrane damage to develop in total ischaemia) and the plasmalemma remained intact by electron microscopy. Thus, despite depletion of high energy phosphates, membrane damage, detectable by alterations in IDS or ultrastructure, occurs much more slowly during anoxia alone than during ischaemia. These results suggest that anoxia, per se, may not be the cause of membrane damage in ischaemia.

Animals↗
PubMed1982

Evaluation of a QRS scoring system for estimating myocardial infarct size. II. Correlation with quantitative anatomic findings for anterior infarcts.

The ability of an independently developed QRS point score to estimate the size of infarcts predominantly within the anterior third of the left ventricular was evaluated by quantitative pathologic-electrocardiographic correlation. The study was limited to 21 patients with a single infarct documented by postmortem examination, for whom an appropriately timed standard 12 lead electrocardiogram was available that did not exhibit signs of left or right ventricular hypertrophy, left or right bundle branch block or anterior or posterior fascicular block. At necropsy the heart was cut into five to seven slices. The location and size of the infarct was quantitated by computer-assisted planimetry of the slices. The electrocardiogram of 19 (90 percent) of the patients exhibited either a Q wave or an R wave of no more than 20 ms in lead V2. The infarct in the two patients without this electrocardiographic finding was small, occupying 2 and 3 percent of the left ventricle, respectively. The percent infarction of the left ventricle correlated with the QRS point score (r=0.80). Thus in patients without complicating factors in the electrocardiogram and with a single infarct, the electrocardiogram provides a marker for infarction in the anterior third of the left ventricle and permits estimation of infarct size.

Adult↗
PubMed1981

Effect of coronary occlusion site on ischaemic bed size and collateral blood flow in dogs.

The ischaemic bed size (myocardium at risk) and collateral flow are major determinants of experimental myocardial infarct size. These parameters were compared in dogs with coronary occlusions at four commonly used sites. Regional blood flow was measured 5 min after proximal coronary occlusion of the circumflex (LCC) or anterior descending (LAD) arteries, or after distal occlusion of the LAD, or its apical branch. Occlusions were done sequentially in random order separated by 30 min intervals. The anatomic regions normally supplied by each occluded artery (ischaemic beds) were identified by simultaneous postmortem coronary perfusion with different coloured dyes. Proximal occlusions of the LCC and LAD produced equivalent areas of ischaemia (37 and 36% of the left ventricle) and these ischaemic beds had similar amounts of collateral flow (0.12 and 0.16 cm3.min-1.g-1). In comparison, distal LAD and apical branch occlusions involved 23 and 11% of the LV and collateral flow averaged 0.23 and 0.36 cm3.min-1.g-1. Thus, proximal LAD or LCC occlusion produce comparable areas of severe ischaemia. Experimental models using distal occlusions are characterised by more variable but often less severe ischaemia.

Animals↗
PubMed1981

Energy metabolism in the reversible and irreversible phases of severe myocardial ischemia.

In summary, myocardial ischemia is associated with the progressive depletion of HEP and the adenine nucleotide pool. Anaerobic glycolysis is essential for energy production in the severely ischemic myocyte and accounts for 80% of the HEP utilized by severely or totally ischemic myocardium. However, the rate of anaerobic glycolysis is too slow to prevent the progressive depletion of ATP. Anaerobic glycolysis stops entirely prior to the complete utilization of glycogen. Without remaining HEP stores or HEP production from anaerobic glycolysis, HEP utilization no longer can occur. This point occurs in vivo after about 40 minutes of severe ischemia and coincides with the onset of cell death. Modest depletion of ATP due to brief periods of transient ischemia may not cause cell death, but is associated with partial depletion of the adenine nucleotide pool. The slow repletion of this pool may be responsible for prolonged depression of contractile function.

Adenine Nucleotides↗