摘要:

Seventeen patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were treated with heparin combined with intravenous singlechain urokinase-type plasminogen activator (scu-PA), obtained by expression of the cDNA encoding mature human scu-PA in Escherichia coli. In eight patients, recombinant scu-PA (rscu-PA) was given as a 10 mg bolus followed by 30 mg over 1 hr. Recanalization was obtained in six patients, but with persistent delayed opacification of the vessel in four of these patients. During infusion, a plateau level of rscu-PA antigen in plasma of 3.4 gtg/ml (median value, range 1.4 to 5.5) was reached. At the end of the infusion the a2-antiplasmin level had decreased to 54% (median, range 22% to 82%) of the preinfusion level, the fibrinogen level to 89% (median, range 26% to 101%), and fibrinogen degradation products (FDPs) to 20, g/ml (median, range 8 to 387). In nine patients, rscu-PA was administered as a 10 mg bolus followed by 60 mg over 1 hr. This resulted in recanalization with normal distal filling of the vessel in seven patients, within 46 17 min (mean + SD). During infusion the concentration of rscu-PA in plasma increased to a median value of 7.4, ug/ml (range 4.0 to 13.3). At the end of the infusion the a2-antiplasmin level was 22% of baseline (range 5% to 47%), the fibrinogen level 45% (range 4% to 94%), and the concentration of FDPs 87 gg/ml (range 6 to 1034). No significant bleeding or short-term side effects were observed. After the end of the infusion the disappearance of rscu-PA antigen from plasma in both groups could be described as a sum of two exponential terms. Ninety-five percent of the plasma disappearance occurred with a tl/2 of 7.9 min and 5% with a: tl/2 of 48 min. Thus intravenous rscu-PA at a sufficiently high infusion rate can produce fibrin-specific coronary thrombolysis in patients with acute myocardial infarction. However, its infusion is associated with a variable degree of systemic fibrinolytic activation, which particularly at higher infusion rates. may result in extensive fibrinogen breakdown,

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

In a porcine preparation of cardiac arrest, we demonstrated that there is a marked paradox of venous acidemia and arterial alkalemia. This paradox is related to decreased clearance of CO2 from the lungs when pulmonary blood flow is critically reduced. Accordingly, increased venous Pco2 rather than metabolic acidosis due to lactic acidosis predominates during the initial 8 min of cardiopulmonary resuscitation. Arterial blood gases fail as indicators of systemic acid-base status and therefore as indicators of tissue acidosis.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

We examined rapid ventricular cardiac pacing as a means of inducing heart failure in the dog to establish the sequence and nature of physiologic compensation in this preparation. Seven animals paced at 250 beats/min for 3 weeks (VP8 group) showed an increase in cardiac size from 78.5 + 9.5(SD) to 105.8 ± 13.0 cm2, a reduction in mean arterial pressure from 149 ± 7 to 130 ± 21 mm Hg, a fall in cardiac index from 196 ± 57 to 125 ± 37 ml/kg/min, and an increase in left ventricular filling pressure from 6 + 5 to 22 + 9 mm Hg and in right atrial pressure from 2 ± 2 to 5 ± 3 mm Hg. An additional series of six animals (VP2 group) was paced until a clear biologic end point for heart failure was reached (average 5.3 + 1.9 weeks) and they showed similar but more advanced changes compared with the VP8 group. The changes in cardiac size and hemodynamics in the VP1 and VP2 groups were significantly different from those in parallel studies of 10 sham-operated animals. Plasma norepinephrine and renin activity were unchanged in sham-operated animals, whereas in the VP1 group, plasma norepinephrine rose from 338 + 118 to 764 ± 567 pg/ml (p < .05), but plasma renin activity did not change. In the VP2 group norepinephrine rose from 471 ± 285 to 999 ± 425 pg/ml (p < .025) and plasma renin rose from 2.1 1.5 to 8.0 ± 7.1 ng/ml/hr (p < .05). There was an excellent correlation between plasma norepinephrine and renin activity before the animals were killed in both the VP1 and VP2 groups (r = .88, p < .001). No change was evident in atrial natriuretic factor content, as determined by bioassay, in sham-operated or VP1 group animals. However, there was a significant reduction in atrial natriuretic activity from the right atrium that was inversely correlated with the level of right atrial pressure in the VP2 group.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

This study tested the hypothesis that a reduction in blood viscosity by means of isovolumetric hemodilution will permit an increase in maximal oxygen delivery to myocardium distal to a moderate coronary arterial stenosis. It is known that blood viscosity is a determinent of resistance to blood flow at both the stenotic and the arteriolar levels. Accordingly, a reduction in blood viscosity could exert a favorable influence on maximal myocardial oxygen delivery in the setting of stenosis, provided that the oxygen-carrying capacity of the blood is not compromised excessively. Closed-chest, sedated domestic swine (n = 8) were instrumented with an artificial coronary arterial stenosis that reduced vessel diameter by 64%. Measurements of hemodynamics, regional myocardial blood flow (microspheres), lactate and oxygen metabolism, and whole blood viscosity were made at control and after two successive 10 min intracoronary infusions of adenosine (400 and 800, ug/min) distal to the stenosis. Next, albumin/saline solution was given intravenously to reduce the animal's hematocrit by approximately 50%. Repeat measurements of all experimental variables were then made at a second control and again after two successive 10 min intracoronary infusions of adenosine (400 and 800 gg/min) distal to the stenosis. Myocardial blood flow (ml/min/g) distal to the stenosis increased from 1.52 + 0.21 (mean 1 SD) to 4.10 0.86 in response to adenosine (peak dose) before hemodilution (p < .01) and from 2.07 + 0.59 to 4.08 + 0.93 (p < .01) after hemodilution. Minimum resistance (mm Hg/ml/min/g) distal to the stenosis, however, was approximately 33% lower (p < .05) during infusion of adenosine after hemodilution than it was before hemodilution (endocardium 15.8 6.3 vs 24.5 14.1 and epicardium 9.0 ± 2.3 vs 14.0 ± 8.0). Maximal oxygen delivery (ml/min/lOOg) to myocardium distal to the stenosis failed to improve and in fact was reduced (p < .01 vs before hemodilution) after hemodilution (34.6 ± 9.5 vs 19.9 ± 6.8 to endocardium and 65.5 ± 16.4 vs 38.0 + 10.5 to epicardium). Regional myocardial lactate metabolism, however, did not change vs initial control during the study. Finally, hematocrit was reduced from 32 3% to 17 + 3% (p < .01) and blood viscosity was reduced from 3.4 ± 0.2 to 2.4 ± 0.3 centipoise (p < .01) by hemodilution. The results of the study indicate that reducing blood viscosity by isovolumetric hemodilution may not enhance maximal myocardial oxygen delivery in the setting of a moderate coronary arterial stenosis. However, because minimal endocardial resistance is lowered by a reduction in blood viscosity, it is likely that maximal oxygen delivery could be improved by this intervention if hemodilution were accomplished with a fluid capable of transporting oxygen (e.g., perfluorocarbon emulsion).

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

This study was designed to determine whether a quantitative analysis of integrated backscatter amplitude distribution is potentially useful in characterizing the atherosclerotic lesion. One hundred measurements (10 x 10 array) were made in fresh aortic regions (2 cm X 2 cm) of nine normal and 19 atherosclerotic arterial walls. A 10 MHz transducer was used. The integrated backscatter distinguished normal from atherosclerotic specimens (−56.7 + 4.3 vs −42.5 + 8.9 dB, p < .01). The shape of the integrated backscatter amplitude distribution was analyzed by calculation of skewness and kurtosis of each arterial region. Both skewness values (0.134 + 0.325 vs − 0.193 + 0.491 in normal and atherosclerotic segments, respectively, p = NS) and kurtosis values (0.055 0.765 vs −0.610 0.379, p < .01) discriminated between the two groups. When only the six atherosclerotic specimens with mostly fatty and fibrofatty sites were considered, skewness and kurtosis still distinguished normal from atherosclerotic regions (0. 134 0.325 vs −0.404 + 0.232, p < .05 and 0.055 + 0.765 vs −0.558 ± 0.337, p < .05, respectively), while integrated backscatter values did not (−56.7 ± 4.5 vs −52.3 ± 6.1 dB, p = NS). In conclusion, atherosclerosis may be detected in vitro by the quantitative analysis of integrated backscatter distribution. This variable could also be of help in the identification of less obvious forms of atherosclerotic disease that are not distinguishable on the basis of integrated backscatter amplitude.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The absolute cross-sectional area of a coronary stenosis measured by quantitative coronary angiography correlates well with its hemodynamic significance. We evaluated a combined approach using edge detection applied to the normal segment and videodensitometry applied to the stenosis to determine the absolute cross-sectional area of the stenosis (videodensity method). The results were then compared with those with the edge detection method applied directly to the stenosis. The area of the stenosis by the edge detection method was calculated by analyzing two orthogonal projections for irregular stenoses and with use of the formula for the area of an ellipse (ellipse method). The accuracy of both these techniques was assessed by analyzing digital angiograms acquired from closed-chest dogs in which 10 plastic cylinders with precisely machined circular and irregular lumina were inserted into the coronary arteries. Angiograms of irregular stenoses were acquired in two orthogonal views. The ellipse method applied to circular stenoses was very accurate, with r = .97, average absolute difference (AAD) = 0.21 mm2, and SEE = 0.30. For the videodensity method r = .97, AAD= 0.84 mm2, and SEE = 0.40. Irregular stenoses were better quantitated by the videodensity method applied in one view (AAD = 0.50 mm2, SEE = 0.47) than by the ellipse method applied in two orthogonal projections (AAD = 1.03 mm2, SEE = 0.87). Overall, the two methods were comparable in accuracy (for videodensity, AAD = 0.65 mm2, SEE = 0.71 vs AAD = 0.54 mm2, SEE = 0.79 for ellipse). Although the ellipse method is more accurate for circular stenoses, the videodensity method has the advantage of quantitating the full range of shapes of stenosis in only one projection.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The left ventricular end-systolic pressure-volume relation has received intense interest as a relatively load-insensitive measure of cardiac performance. In clinical studies, pharmacologic manipulation of blood pressure has been used to determine this relation. Since previous studies have shown that acute changes in the resistance and impedance of the arterial circulation influence the left ventricular end-systolic pressure-volume relation, the use of vasoactive drugs in its determination may affect the results achieved. This study was undertaken to determine whether clinically used vasoactive drugs influence the left ventricular end-systolic pressure-volume relation. Sixteen dogs were previously instrumented with micromanometer pressure transducers and three sets of piezoelectric crystals to permit determination of left ventricular pressure and volume. The dogs were studied after autonomic blockade and sedation. End-systolic pressure-volume relations were generated by caval occlusion at control levels of blood pressure, after infusion of a vasopressor (methoxamine, n = 6; angiotensin II, n = 10), and then after infusion of nitroprusside. A composite end-systolic pressure-volume relation was also constructed with the use of control, vasopressor, and vasodilator points in each dog. Angiotensin LI resulted in a leftward shift in the relation (VO decreased from 14.32 + 7.3 to 8.04 ± 10.4 ml, p < .05) with no significant effect on slope. Methoxamine shifted the relation to the left (VO decreased from 13.98 + 8.74 to − 0.47 + 12.06 ml, p < .05) and also reduced the slope (5.41 ± 3.09 vs 8.28 + 3.94 mm Hg/ml, p < .05). Nitroprusside shifted the relation to the right (VO increased from 13.98 ± 8.74 to 17.35 ± 11.04 ml, p < .05), but did not significantly alter the slope. The composite end-systolic pressure-volume relations in the animals given angiotensin II had a steeper slope (11.22 ± 4.87 mm Hg/ml, p < .05) and were shifted to the right (17.99 ± 8.41 ml, p < .05) compared with those generated by control caval occlusion. The composite relations in the animals given methoxamine, on the other hand, had a flatter slope (7.15 + 3.13 mm Hg/mI, p < .05), with no significant difference in VO compared with control caval occlusion. We conclude that the technique used to generate the left ventricular end-systolic pressure-volume relation influences the results that are obtained. Results obtained through the use of pharmacologic alteration of load are different than those obtained with use of rapid caval occlusion, and vary depending on the vasoactive agents used. These factors should be considered when interpreting the findings of studies on this index of cardiac performance.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Systemic vascular resistance (SVR) is a frequently used clinical index of left ventricular afterload. However, SVR may not adequately assess left ventricular afterload (i.e., ventricular internal fiber load during systole) since it reflects only peripheral vasomotor tone. In contrast, left ventricular end-systolic wall stress (ces) reflects the combined effects of peripheral loading conditions and left ventricular chamber pressure, dimension, and wall thickness. To determine the relationship between SVR and cyes, left ventricular afterload and contractility were pharmacologically altered in eight dogs instrumented with central aortic microtip and Swan-Ganz thermodilution catheters. Left ventricular wall thicknesses and dimensions were measured from two-dimensionally targeted M mode echocardiograms. Aortic, right atrial, and left ventricular end-systolic pressures as well as cardiac output were recorded. SVR and aes were determined under control conditions as well as during infusions of nitroprusside, methoxamine, dobutamine, and norepinephrine. Control data acquired before each drug infusion were similar. When compared with baseline values, SVR underestimated the magnitude of change in left ventricular Cyes by (1) 22% when afterload alone was decreased (nitroprusside), (2) 54% when afterload alone was increased (methoxamine), and (3) 50% when afterload was decreased and contractility was augmented (dobutamine). Most importantly, when afterload was minimally decreased in association with augmented contractility (norepinephrine), SVR increased by 21% while, es fell by 9%. Thus, discordant changes in left ventricular afterload (i.e., a,) and SVR can occur during pharmacologic interventions. SVR is an unreliable index of left ventricular afterload, reflecting only peripheral arteriolar tone rather than left ventricular systolic wall force. This emphasizes the fact that a true measure of left ventricular afterload must consider the interaction of factors internal and external to the myocardium.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

We have previously shown that a brief episode of ischemia slows the rate of ATP depletion during subsequent ischemic episodes. Additionally, intermittent reperfusion may be beneficial to the myocardium by washing out catabolites that have accumulated during ischemia.1Thus, we proposed that multiple brief ischemic episodes might actually protect the heart from a subsequent sustained ischemic insult. To test this hypothesis, two sets of experiments were performed. In the first set, one group of dogs (n = 7) was preconditioned with four 5 min circumflex occlusions, each separated by 5 min of reperfusion, followed by a sustained 40 min occlusion. The control group (n = 5) received a single 40 min occlusion. In the second study, an identical preconditioning protocol was followed, and animals (n = 9) then received a sustained 3 hr occlusion. Control animals (n = 7) received a single 3 hr occlusion. Animals were allowed 4 days of reperfusion thereafter. Histologic infarct size then was measured and was related to the major baseline predictors of infarct size, including the anatomic area at risk and collateral blood flow. In the 40 min study, preconditioning with ischemia paradoxically limited infarct size to 25% of that seen in the control group (p < .001). Collateral blood flows were not significantly different in the two groups. In the 3 hr study, there was no difference between infarct size in the preconditioned and control groups. The protective effect of preconditioning in the 40 min study may have been due to reduced ATP depletion and/or to reduced catabolite accumulation during the sustained occlusion. These results suggest that the multiple anginal episodes that often precede myocardial infarction in man may delay cell death after coronary occlusion, and thereby allow for greater salvage of myocardium through reperfusion therapy.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Isolated preparations of rabbit interventricular septum were perfused through the coronary arteries with oxygenated Tyrode's solution and placed in a tissue bath where they were superfused as well. Transmembrane potentials were simultaneously recorded from the subendocardium with two flexibly mounted microelectrodes, one from a superficial cell, and the other from a deep cell. Ischemia was produced by stopping coronary flow while superfusion with oxygenated Tyrode's solution was maintained. After a 7 to 12 min ischemic period, the preparation was fixed by coronary perfusion with fixative while the microelectrodes remained in place. After fixation, the microelectrodes were withdrawn. Appropriate tissue blocks were cut in 4, gm serial sections and the microelectrode track was followed until the tip position was identified. Transmembrane potentials during ischemia were divided into two categories: (1) “border zone” potentials (resting membrane potential [RMP] 73 + 3 mV, action potential amplitude [APA] 81 + 13 mV, action potential duration [APD] 116 + 48 msec, n = 12) and (2) “ischemic” potentials (RMP 53 ± 4 mV, APA 44 ± 11 mV, APD 102 ± 42 msec, n = 8). Ischemic potentials were recorded from cells at depths greater than 560 pum below the endocardial surface and border zone potentials were recorded in a layer at between 130 and 650 μm below the surface. In a separate series of experiments, extracellular concentrations of K+ and pH were measured with ion-sensitive electrodes at different depths and, after a 10 min period of ischemia, part of the septum was placed in liquid nitrogen to allow determination of phosphocreatine (PC) levels in successive 50 to 100, um layers. After 10 min of ischemia, extracellular K+ gradually increased from 4 to 9 mM in endocardium to a depth of 600 gim, pH fell from 7.4 to 6.6 over the same distance, and PC decreased to very low, stable levels at only 800 gim. It is concluded that in the first 10 min of acute ischemia, an endocardial border zone exists of 40 to 60 cell layers in which transmeimbrane potentials are affected relatively little by ischemia. Within this electrophysiologic border zone extracellular K+ was lower than 9 mM, pH was higher than 6.6, and tissue content of PC was not lower than 40% of normal. In layers deeper than 600 gim, with further development of a metabolic gradient, action potentials became markedly depressed. This electrophysiologic inhomogeneity within the ischemic subendocardium could be a factor in arrhythmogenesis during the first minutes of ischemia.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID