Influence of heart rate, preload, afterload, and inotropic state on myocardial ultrasonic backscatter

Ultrasonic backscatter is substantially modified by pathologic changes in myocardium. Influence of physiologic changes in heart rate, mean arterial pressure, preload, and inotropic state were studied in 17 anesthetized open-chest dogs. Heart rate was changed with atrial pacing/ULFS'49 (a selective bradycardiac agent). Mean arterial pressure was varied with aortic constriction/nitroprusside, preload was altered with nitroglycerin/volume infusion, and inotropic states were altered with dobutamine (10 microns/kg)/esmolol (100 microns/kg). IBR5, an optimum weighted frequency average (4 to 6.8 MHz) of the squared envelope of diffraction corrected for absolute backscatter, and the Fourier coefficient of amplitude modulation (FAM), an index of cardiac cycle-dependent variation, were measured from six sequential electrocardiographically gated intervals throughout the cardiac cycle. Heart rate, mean arterial pressure, preload, and inotropic state did not significantly affect IBR5. FAM increased from 3.5 +/- 0.3 dB (mean +/- SEM) to 7.0 +/- 0.4 dB (p less than .01) at a heart rate of 120 beats/min, and decreased to 3.9 +/- 0.4 at a heart rate of 160 beats/min. No change in FAM was noted with a rise (70 +/- 12 to 45 +/- 10 mmHg) in mean arterial pressure or preload (an increase or decrease in diastolic segment length of +/- 10% from the baseline). Dobutamine produced a significant increase in left ventricular dP/dt (2600 +/- 200 to 3475 +/- 275 mm Hg) and FAM (3.4 +/- 0.1 to 6.4; p less than .01). Esmolol significantly reduced left ventricular dP/dt (2600 +/- 200 to 2000 +/- 175 mm Hg, p less than .05) and FAM (3.4 +/- 0.01 to 6.4 +/- 0.1; p less than .01). We conclude that IBR5 is independent of heart rate, mean arterial pressure, preload, and inotropic state. Cardiac cycle-dependent amplitude modulation follows changes in cardiac contraction.     

Deleterious cardiac effects of captopril during acute myocardial ischaemia in the dog.

OBJECTIVE: The aim was to evaluate the effects of the angiotensin converting enzyme inhibitor captopril on acute myocardial ischaemia. METHODS: Seventeen anaesthetised open chest dogs were randomised to 3 minute angioplasty balloon occlusions of the left circumflex coronary artery before and after intravenous infusion of captopril (n = 8) or placebo (n = 9). RESULTS: There was apparent worsening of ischaemia during balloon inflation after captopril infusion, when compared with control inflation, as suggested by further ST segment elevation of 1.8 (SD 1.8) mm, p less than 0.03, and by further lowering of regional myocardial pH [-0.05(0.05), p = 0.06], and peak positive and peak negative dP/dt [-439(337)mm Hg.s-1, p less than 0.008; -470(316) mm Hg.s-1, p less than 0.004, respectively]. The increase in ischaemia occurred despite reduced double product after captopril administration. Regional myocardial blood flow in the ischaemic artery distribution was lower during post captopril balloon occlusion [-0.1(0.06) ml.min-1.g-1, p less than 0.005] than during control balloon inflation, while coronary vascular resistance increased by 161(172)% (range 45 to 497%, p less than 0.04). There were no significant differences in ST segments, pH, haemodynamic variables, or blood flow during balloon inflations before and after saline infusion. CONCLUSIONS: Despite lower myocardial metabolic demands, acute intravenous administration of captopril was associated with increased ischaemia during transient coronary artery occlusion.     

Reduced prostaglandin release from the stunned porcine heart--significance for attenuated reactive hyperaemia

STUDY OBJECTIVE--Since both reactive hyperaemia and membrane phospholipids are altered even after short lasting ischaemic periods, the release of PGE2 and PGI2 in the basal state and during early reperfusion was examined to determine whether it was changed in the stunned myocardium. The effect of prostaglandin synthesis inhibition on reactive hyperaemia was also examined. DESIGN--The distal left anterior descending coronary artery was occluded for brief periods and coronary flow was recorded by Doppler flowmetry. In subgroups: (1) a shunt was established draining the ischaemic region for determination of myocardial prostaglandin release associated with 2 min of ischaemia before and after a 10 min occlusion; (2) prostaglandin synthesis was blocked between two 2 min occlusions by infusing indomethacin into the left anterior descending artery; and (3) segment lengths were measured in the left anterior descending artery region subjected to consecutive periods of 2, 10, and 2 min of ischaemia, and in a control region. EXPERIMENTAL MATERIAL--21 pentobarbitone sodium anaesthetised pigs, weight 21-30 kg, were used. MEASUREMENTS AND MAIN RESULTS--30 min after the 10 min occlusion, systolic shortening was reduced by 38(18-57)% (median +95% confidence interval; p less than 0.05). Concomitantly, basal PGE2 and PGI2 release was reduced by 69(30-77)% (p less than 0.05) and 58(7-81)% (p less than 0.05), respectively. During early reperfusion after 2 min of ischaemia, PGE2 release was reduced by 53(17-86)% (p less than 0.05) after development of stunning, whereas PGI2 release remained unaltered. Blockade of prostaglandin synthesis did not affect reactive hyperaemia either in normal or in stunned myocardium. CONCLUSIONS--Prostaglandin release from the stunned myocardium is reduced. Since indomethacin did not affect reactive hyperaemia, the attenuated PGE2 release during early reperfusion in stunned myocardium cannot explain the concomitant reduction in reactive hyperaemia.     

Ultrasonic backscatter and collagen in normal ventricular myocardium

Integrated ultrasonic backscatter has been related to collagen deposition in fibrotic myocardium. The purpose of our study was to measure the integrated ultrasonic backscatter in the right and left ventricles of 10 normal freshly excised canine hearts and five normal formalin-fixed human hearts. A 2.25 MHz, 50% fractional bandwidth transducer was positioned at the transducer focal distance from the epicardium. The radio frequency backscatter signal, excluding specular reflections, was digitized, squared, and integrated to yield the integrated ultrasonic backscatter (in decibels down from a 100% reflector). The segment of myocardium corresponding to the integrated ultrasonic backscatter sample volume was excised and assayed for hydroxyproline, a marker for collagen. A second purpose of our study was to evaluate the influence of fixation with formalin on the backscatter. Regional integrated ultrasonic backscatter was therefore measured in 10 freshly excised canine left ventricles, which were fixed in 10% formalin for 2 weeks. Integrated ultrasonic backscatter measurements were then repeated. In freshly excised canine hearts, the integrated ultrasonic backscatter from right ventricle was higher than that from left ventricle (-60.4 +/- 1.6 [SEM] vs -66.9 +/- 1.0 dB; p less than .001). The collagen content of right ventricle was also higher than that of left ventricle (4.40 +/- 0.26 [SEM] vs 3.58 +/- 0.13 micrograms/mg dry weight; p less than .005). Similar results were obtained in human hearts. There were no correlations between integrated ultrasonic backscatter and collagen content (r = .28 and .32 for dogs and humans, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of acute experimental left ventricular thrombi with quantitative backscatter imaging

Two-dimensional echocardiography is an excellent technique for detecting left ventricular thrombi, however, acute clot is sometimes difficult to differentiate from adjacent myocardium and intracavitary signals. We hypothesized that quantitative assessment of the acoustic properties of acute left ventricular thrombi using a quantitative backscatter imaging system would permit the differentiation of thrombus from adjacent myocardium and intracavitary echoes. Acute, experimental left ventricular thrombi in seven dogs were evaluated with a quantitative backscatter imaging system that allowed the measurement of relative integrated backscatter and cyclic (i.e., diastolic minus systolic) variation in integrated backscatter. Coronary ligation abolished the cyclic variation in relative backscatter that occurred in normal myocardium. The end-diastolic relative backscatter in the thrombus (16.9 +/- 1.3 dB) was significantly higher than in apical myocardium (13.2 +/- 0.6 dB, p less than 0.05). There was no significant difference in the cyclic variation in relative backscatter among thrombus, ischemic myocardium, or intracavitary blood. Thus, the quantitative assessment of the acoustic properties of left ventricular thrombi can be useful in their detection and in the differentiation from myocardium and intracavitary signals.     

Anti-arrhythmic effects of amiodarone and desethylamiodarone on malignant ventricular arrhythmias arising as a consequence of ischaemia and reperfusion in the anaesthetised rat

The effects of amiodarone and its metabolite desethylamiodarone on arrhythmias induced by ischaemia and reperfusion were studied in vivo in the anaesthetised rat with transient regional ischaemia (7 min of left coronary artery occlusion) and reperfusion (10 min). Amiodarone or desethylamiodarone were administered intravenously either 10 min prior to ischaemia or 2 min prior to reperfusion. Control rats received an equivalent volume of vehicle. Administration of 5.0 mg.kg-1 amiodarone or desethylamiodarone prior to ischaemia reduced the incidence of ventricular tachycardia during the ischaemic period from 67% to 20% (p less than 0.02) and 47% respectively. During reperfusion, mortality was reduced from 53% to 7% and 7% (p less than 0.02) respectively, and reperfusion induced ventricular fibrillation from 73% to 20% (p less than 0.01) and 47% respectively. When the drugs were given prior to ischaemia, the plasma concentrations of amiodarone and desethylamiodarone were 1.03 (SEM 0.18) and 0.22(0.02) micrograms.ml-1 and the myocardial concentrations were 23.43(2.78) and 30.41(1.87) micrograms.g-1 respectively. Similar concentrations were found in plasma and myocardium with drugs given prior to reperfusion. No significant differences in plasma or myocardial concentrations of amiodarone or desethylamiodarone were observed between animals which developed ventricular fibrillation and those which did not. In conclusion, this study demonstrates that desethylamiodarone can, like its parent compound, protect the heart against malignant ventricular arrhythmias arising as a consequence of regional myocardial ischaemia and reperfusion.     

Ultrasonic tissue characterization with integrated backscatter. Acute myocardial ischemia, reperfusion, and stunned myocardium in patients

We have previously shown in studies of experimental animals that myocardium exhibits a cardiac cycle-dependent variation of integrated backscatter that reflects regional myocardial contractile performance and that is blunted promptly after arterial occlusion and recovers after reperfusion. To define the clinical utility of ultrasonic tissue characterization with integrated backscatter for detection of acute myocardial infarction and reperfusion, 21 patients (14 men and seven women) were studied in the cardiac care unit within the first 24 hours (mean time, 11.3 hours; range, 3.5-23.8 hours) after the onset of symptoms indicative of acute myocardial infarction with conventional two-dimensional and M-mode echocardiography and with analysis of integrated backscatter. The magnitude of cyclic variation of integrated backscatter was measured from several sites within acute infarct regions and normal regions remote from the infarct zone for each patient. The average magnitude of cyclic variation among all patients (n = 21) was 4.8 +/- 0.5 dB in normal regions compared with 0.8 +/- 0.3 dB in infarct regions (p less than 0.05) within the first 24 hours after the onset of symptoms. Among the patients who had two studies, 15 (mean, 7.1 days; range, 2-31 days for second study) underwent coronary arteriography to define vessel patency. In patients with vessels with documented patency (n = 10), the magnitude of cyclic variation in infarct regions increased over time from 1.3 +/- 0.6 to 2.5 +/- 0.5 dB from the initial to final study (p less than 0.05). Patients with occluded infarct-related arteries (n = 5) exhibited no significant recovery of cyclic variation (0.3 +/- 0.3-0.6 +/- 0.3 dB). A blinded analysis of standard two-dimensional echocardiographic images revealed no significant recovery of wall thickening in either group over the same time intervals. Ultrasonic tissue characterization promptly detects acute myocardial infarction and may delineate potential beneficial effects of coronary artery reperfusion manifest by restoration of cyclic variation of integrated backscatter in the presence of severe wall motion abnormalities.     

Hypoxic preconditioning of ischaemic canine myocardium.

OBJECTIVE: The aim was to test whether a brief period of non-ischaemic hypoxia can precondition myocardium. METHODS: 60 anaesthetised adult mongrel dogs of either sex underwent 60 min occlusion of the left anterior descending coronary artery, followed by 5 h reperfusion. In treated groups, hearts were either preconditioned with 5 min coronary perfusion with hypoxic blood [O2 content 9.2(SEM 0.6) ml.litre-1] or 5 min occlusion followed by a 10 min reperfusion period prior to 60 min occlusion. The effect of these treatments on myocardial infarct size and regional contractile function was assessed. RESULTS: Infarct size, determined by tetrazolium staining, as a percentage of anatomical area at risk was markedly decreased in hypoxia preconditioned hearts, at 7.2(1.8)% v 22.4(4.6)% in controls (p < 0.01), but did not differ from ischaemia preconditioned hearts [4.6(1.7)%; p < 0.01 v control]. Anatomical area at risk, expressed as a percentage of left ventricular mass, and collateral blood flow to the inner two thirds of the ischaemic wall did not differ among the groups. Regional contractile function was depressed following ischaemic preconditioning but not following hypoxic preconditioning. During reperfusion following 60 min occlusion, marked paradoxical systolic lengthening was evident in ischaemia preconditioned and control hearts but not in hypoxia preconditioned myocardium. CONCLUSIONS: Five minutes of hypoxic and ischaemic preconditioning were equipotent in preventing infarction, whereas ischaemic preconditioning caused a greater decrement in postischaemic contractile function.     

The use of frequency histograms of ultrasonic backscatter amplitudes for detection of atherosclerosis in vitro

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 less than .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 less than .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 less than .05 and 0.055 +/- 0.765 vs -0.558 +/- 0.337, p less than .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.     

Effects of coronary artery occlusion and reperfusion on cardiac cycle-dependent variation of myocardial ultrasonic backscatter

We have recently reported a systematic variation in integrated ultrasonic backscatter throughout the cardiac cycle in canine hearts. This study was performed to determine whether the pattern of such variation is modified systematically by ischemia. Measurements of integrated ultrasonic backscatter in selected regions of normal, ischemic, and reperfused hearts were compared in view of known differences in systolic function of myocardium in each of these regions. Integrated ultrasonic backscatter (3-7 MHz) gated to the first derivative of left ventricular pressure was measured at the apex, midwall, and base in 10 dogs and at the apex before and during transient ischemia and reperfusion in four dogs. Quantitative integrated ultrasonic backscatter was referenced to a steel reflector. Cyclic variation of integrated ultrasonic backscatter was greatest at the apex [peak to trough variation 5.5 +/- 0.9 dB (mean +/- SE)] with the maximum near end diastole (-52.9 +/- 0.9 dB) and minimum near end systole (-58.4 +/- 1.0 dB). Variation at the apex (5.5 +/- 0.9 dB) and the midwall (4.3 +/- 0.8 dB) was greater than at the base (0.5 +/- 1.0 dB) (P less than 0.01 for either region compared with base). Left anterior descending coronary occlusion for 10 minutes in four of 10 dogs reduced variation at the apex to 0.4 +/- 1.5 dB (P less than 0.02 compared with preocclusion). Reperfusion for 2 hours restored apical cyclic variation to 3.9 +/- 1.7 dB, i.e., to values not significantly different from those before occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of anaesthesia on acute ischaemic arrhythmias and epicardial electrograms in the pig heart in situ.

STUDY OBJECTIVE--The aim of the study was to assess the influence of general anaesthesia on electrocardiographic and arrhythmogenic responses to left anterior descending coronary artery occlusion. DESIGN--Pigs weighing 18-20 kg were anaesthetised with alpha chloralose 100 mg.kg-1 (n = 9) or thiopentone 30 mg.kg-1 (n = 9) and the arrhythmogenic effects of coronary artery occlusion were examined by sequential electrocardiographic measurements every 5 min and arrhythmia analysis every minute over a 60 min period. RESULTS--alpha Chloralose predisposed to lower ST segment elevation (analysis of variance for repeated measurements p less than 0.002), less marked epicardial conduction delay (p less than 0.01) with slower progression to monophasic potentials, and in contrast, to a greater number of episodes of ventricular premature beats (p less than 0.005), ventricular tachycardia (51 v 32 episodes), and ventricular fibrillation (6 v 2 pigs) than barbiturate anaesthesia. CONCLUSIONS--alpha Chloralose and barbiturates exerted opposite electrocardiographic and arrhythmogenic effects in a porcine model of acute myocardial ischaemia. Due to its proarrhythmic effect chloralose should probably be used in studies dealing with spontaneous and induced ischaemic arrhythmias.     

Improvement in contractile recovery of isolated rat heart after cardioplegic ischaemic arrest with endogenous phosphocreatine: involvement of antiperoxidative effect?

STUDY OBJECTIVE--The aim was to attempt to get further insight into the mechanism of the cardioprotective action of phosphocreatine (PCr). DESIGN--Three experimental protocols were used: (1) The effect was examined of exogenous PCr (10 mmol.litre-1) on myocardial oxidative damage produced by H2O2 perfusion (90 mumol.litre-1) of isolated rat heart. (2) Isolated rat hearts were subjected to 35 min cardioplegic ischaemia followed by reperfusion. A control group was studied along with two PCr groups, one corrected for Ca2+ to compensate its binding with PCr (1.4 mmol.litre-1 CaCl2 in St Thomas's Hospital cardioplegic solution), and the other not (1.2 mmol.litre-1). (3) The effect was studied of PCr alone and in combination with the antioxidant tocopherol phosphate (0.1 mumol.litre-1) on contractile and metabolic recovery of isolated rat heart reperfused after 40 min cardioplegic ischaemia. EXPERIMENTAL MATERIAL--Studies were performed on hearts of 84 male Wistar rats, weighing 250-300 g. MEASUREMENTS AND MAIN RESULTS--(1) Oxidative stress resulted in irreversible contracture and impairment of sarcolemmal integrity revealed by using the transmembrane tracer ionic lanthanum. These effects coincided with the decrease of developed pressure from 116 (SEM 3) to 38(3) mm Hg and rate-pressure product from 498(13) to 165(16) mm Hg.s-1. The Ca2+ binding property of PCr was estimated experimentally and the stability constant of the complex CaPCr was found to be 35.4(0.7) mmol; from this the Ca2+ bound by PCr was calculated to be 14% in the experimental conditions used. Ca2+ concentration in K-H buffer containing PCr was increased to compensate its binding with PCr. PCr prevented H2O2 induced contracture, preserved sarcolemmal integrity, and attenuated H2O2 induced decrease in developed pressure and rate-pressure product [73(6) mm Hg and 340(28) mm H.s-1, respectively, p less than 0.05 compared with control]. (2) PCr reduced the diastolic pressure [29(10) v 68(10) mm Hg in control group at 30 min of reperfusion, p less than 0.05] and enhanced the developed pressure [81(10) v 46(10) mm Hg in controls, p less than 0.05] and rate-pressure product [325(44) v 158(40) mm Hg.s-1 in controls, p less than 0.05]. When CaCl2 was increased to 1.4 mmol.litre-1 the protective effect of PCr was not abolished. (3) PCr resulted in improvement of developed pressure [49(7) v 18(5) mm Hg in controls at 40 min of reperfusion, p less than 0.05] and rate-pressure product [184(27) v 71(20) mm Hg.s-1 in controls, p less than 0.05]. The degree of contractile recovery in the tocopherol group was almost the same as in the PCr group. Combined addition of PCr and tocopherol further increased the developed pressure and rate-pressure product to 72(4) mm Hg and 284(23) mm Hg.s-1, respectively. Similarly, PCr and tocopherol in combination provided substantial inhibition of creatine kinase release into perfusate, at 3.8(0.4) v 10.9(2.5) IU in controls, p less than 0.05. CONCLUSIONS--PCr decreases the vulnerability of myocardium to oxidative stress and ischaemic damage. These effects cannot be explained by PCr induced shifts in Ca2+ concentration. Protective effects of PCr and tocopherol are quantitatively additive, most probably due to their different mechanisms of action, and tocopherol may be effective in extending the ability of PCr to stabilise cell membrane structure.     

The contribution of ischaemia to the development of microvascular incompetence in the myocardium

STUDY OBJECTIVE--The aim was to determine the contribution of ischaemia per se to the development of microvascular incompetence in the myocardium. DESIGN--Isolated, buffer perfused rat hearts were made globally ischaemic for 0-60 min, then fixed with nitrogen bubbled glutaraldehyde and perfused with nuclear track emulsion to identify and quantify competent blood vessels in scanning and transmission electron micrographs. SUBJECTS--Adult Male Wistar rats weighing between 275 and 350 g were used. MEASUREMENTS AND MAIN RESULTS--Thirty or more min ischaemia significantly (p less than 0.05) reduced the density of competent capillaries in the subendocardial third of the myocardium, as did 45 or more min in the subepicardial third and 60 min in the middle third. Following 60 min ischaemia virtually all vessels in the subendocardial third were not perfusable. Severely ischaemic myocardium showed relatively normal, open, unobstructed capillaries and an absence of the endothelial, myocyte and mitochondrial swelling which have previously been attributed to ischaemia. CONCLUSIONS--In severely ischaemic myocardium microvascular incompetence shows a transmural gradient in severity. It develops progressively, starting near the endocardium. These findings suggest that postischaemic reoxygenation may accelerate the development of microvascular incompetence.     

Ultrasonic tissue characterization of human hypertrophied hearts in vivo with cardiac cycle-dependent variation in integrated backscatter

Integrated ultrasonic backscatter (IB) is a noninvasive measure of the acoustic properties of myocardium. Previous experimental studies have indicated that altered acoustic properties of the myocardium are reflected by the magnitude of variation of IB during the cardiac cycle. In our study, cardiac cycle-dependent variation of IB was noninvasively measured using a quantitative IB imaging system in 12 patients with uncomplicated pressure-overload hypertrophy and 13 patients with hypertrophic cardiomyopathy. Sixteen normal subjects served as a control. The magnitude of cardiac cycle-dependent variation of IB for the posterior wall was 6.0 +/- 0.9 dB in normal subjects, 5.7 +/- 0.8 dB in the patients with uncomplicated pressure-overload hypertrophy, and 6.7 +/- 2.1 dB in the patients with hypertrophic cardiomyopathy. There were no significant differences among any of these groups. In contrast, the magnitude of cardiac cycle-dependent variation of IB for the septum was significantly smaller in the patients with uncomplicated pressure-overload hypertrophy (2.8 +/- 1.3 dB) and in the patients with hypertrophic cardiomyopathy (3.1 +/- 2.3 dB) than in normal subjects (4.9 +/- 1.0 dB). The magnitude of cardiac cycle-dependent variation of IB was smaller as the wall-thickness index increased (r = -0.53, p less than 0.01, n = 82 for all data). This IB measure also correlated with percent-systolic thickening of the myocardium (r = 0.67, p less than 0.01, n = 82). Thus, alteration in the magnitude of cardiac cycle-dependent variation of IB was observed in hypertrophic hearts and showed apparent regional myocardial differences.     

Beneficial effects of oxypurinol pretreatment in stunned, reperfused canine myocardium

The mechanism of reperfusion induced injury in acutely ischaemic myocardium is controversial but may be connected with oxygen free radical generation. However, chronic allopurinol treatment has beneficial effects in ischaemic myocardium which are not due to its inhibition of xanthine oxidase induced oxygen free radical production. Allopurinol is rapidly metabolised to oxypurinol, so we have examined the effects of this compound on nutrient blood flow and contractility in a canine model of stunned, reperfused myocardium. Twenty anaesthetised dogs underwent 15 min of total circumflex artery occlusion followed by 15 min restricted reflow and 2 h full reflow. Posterior wall thickening was determined by sonomicrometry and expressed as % control function. Regional myocardial blood flow was measured by microsphere technique and expressed in ml.min-1.g-1. Dogs in the treatment group (n = 10) received 25 mg.kg-1 oxypurinol as a 5 min left atrial infusion, 15 min prior to circumflex occlusion. Controls (n = 10) received a saline infusion. During occlusion mean circumflex pressure (17.6 v 18.2 mm Hg), endocardial flow [0.02(SEM 0.01) v 0.03(0.01) ml.min-1g-1], and area at risk [31.4(1.2%) v 34.6(2.4%)] were similar for both groups (control v treated respectively). Endocardial blood flow increased following acute administration of oxypurinol: 1.57(0.15) v 0.92(0.15) ml.min-1g-1 in control (vehicle) group, p less than 0.05. This effect persisted for the duration of the experiment, with a significant increase during early reflow: 1.83(0.32) v 0.74(.21), p = 0.03. There was also a marked increase in posterior wall function in the treated group, at 54.6(5.5)% v 5.1(8.4)% in the control group (p = 0.0003). These results show that pretreatment with oxypurinol protects acutely ischaemic myocardium, producing enhanced myocardial blood flow, diminished systolic bulge during occlusion, and markedly enhanced function recovery following reperfusion.     

Quantitative ultrasonic characterization of the nature of atherosclerotic plaques in human aorta

To determine the feasibility of quantitative ultrasonic techniques to define the composition of atherosclerotic plaques, samples of freshly excised human aortas were sewn to a sample holder and immersed in a saline bath for ultrasonic interrogation. Integrated backscatter of a 2-microsecond portion of the backscattered radiofrequency signal was measured with a 10 MHz focused transducer. Integrated backscatter was calculated by normalizing the root-mean-square voltage of the gated signal to the root-mean-square voltage obtained by replacing the tissue sample with a nearly perfect reflector. Microscopic examination of the 124 interrogated sites allowed differentiation of normal, fibrous, fibrofatty, and calcified regions. A site was considered calcified if it contained any histochemically detectable calcium. Values of integrated backscatter were markedly elevated from calcified regions (-30.0 +/- 6.4 dB, n = 25; mean +/- SD; p less than 0.001) compared to normal (-43.2 +/- 2.4 dB, n = 20) and fibrofatty (-43.9 +/- 3.4 dB, n = 43) sites. Values from fibrous regions (-40.7 +/- 3.8 dB, n = 36) were also significantly different compared with the calcified and fibrofatty regions (p less than 0.001). Thus, we have demonstrated that quantitative ultrasonic backscatter identifies and differentiates calcification and fibrosis in atherosclerotic sites offering promise for the noninvasive assessment of the pathologic status of the arterial wall.     

Protective effects of preconditioning of the ischaemic myocardium involve cyclo-oxygenase products

STUDY OBJECTIVE--The aim was to determine whether short (preconditioning) occlusions of a coronary artery protect against the arrhythmias occurring during a subsequent more prolonged occlusion and to examine whether the observed protection is mediated by the release of a product of the cyclo-oxygenase pathway of arachidonic acid metabolism. DESIGN--The effects were examined of two short (5 min) coronary artery occlusions, in chloralose-urethane anaesthetised dogs, on a subsequent prolonged (25 min) occlusion; analysis of ischaemia and reperfusion induced arrhythmias and of epicardial ST segment changes was performed. EXPERIMENTAL MATERIAL--46 anaesthetised mongrel dogs in a restricted body weight range were used. MEASUREMENTS AND MAIN RESULTS--Preconditioning reduced the incidence and severity of ischaemic arrhythmias during a 25 min occlusion. Ventricular premature beats (VPB) reduced from 445 (SEM 140) to 96(22) (p less than 0.01), ventricular fibrillation (VF) from 4/10 to 0/20 (p less than 0.05), and ventricular tachycardia from 9/10 to 6/20 (p less than 0.05). VF following reperfusion was reduced from 6/6 to 6/10 (p less than 0.05). Preconditioning thus increased survival from the prolonged ischaemia-reperfusion insult from 0% to 40%. The protective effect of preconditioning was lost in the presence of the cyclo-oxygenase inhibitor sodium meclofenamate (2 mg.kg-1), eg, VPBs 367(95), VF during occlusion 1/9 and during reperfusion 8/8, survival 0%. CONCLUSIONS--Short, preconditioning periods of myocardial ischaemia protect the myocardium against the arrhythmogenic effects of a more prolonged occlusion. That this protection is lost if the cyclo-oxygenase pathway is blocked suggests a protective role for prostanoids, most likely prostacyclin, as endogenous myocardial protective substances.     

Ultrasonic characterization of porcine liver tissue at frequency between 25 to 55 MHz

AIM: To study the relation between acoustic parameters and histological structure of biological tissue and to provide the basis for high-resolution image of biological tissues and quantitative ultrasonic diagnosis of liver disease. METHODS: Ultrasonic imaging and tissue characterization of four normal porcine liver and five cirrhotic liver tissue samples were performed using a high frequency imaging system. RESULTS: The acoustic parameters of cirrhotic liver tissue were larger than those of normal liver tissue. The sound velocity was 1577 m/s in normal liver tissue and 1631 m/s in cirrhotic liver tissue. At 35 MHz, the attenuation coefficient was 3.0 dB/mm in normal liver tissue and 4.1 dB/mm in cirrhotic liver tissue. The backscatter coefficient was 0.00431 dB/Srmm in cirrhotic liver tissue and 0.00303 dB/Srmm in normal liver tissue. The backscatter coefficient increased with the frequency. The high frequency images coincided with their histological features. CONCLUSION: The acoustic parameters, especially the sound backscatter coefficient, are sensitive to the changes of liver tissues and can be used to differentiate between the normal and pathological liver tissues. High frequency image system is a useful device for high-resolution image and tissue characterization.     

Serial measurement of integrated ultrasonic backscatter in human cardiac allografts for the recognition of acute rejection

Cyclic variation of integrated ultrasonic backscatter (IB) was noninvasively measured in the septum and left ventricular posterior wall using a quantitative IB imaging system to assess the alterations in the acoustic properties of myocardium associated with acute cardiac allograft rejection. The study population consisted of 23 cardiac allograft recipients and 18 normal subjects. In each cardiac allograft recipient, one to eight (mean, four) IB studies were performed, each within 24 hours of right ventricular endomyocardial biopsy performed for rejection surveillance. The magnitude of the cyclic variation of IB in the posterior wall was 5.9 +/- 0.9 dB in normal subjects and 6.2 +/- 1.3 dB in the cardiac allograft recipients without previous or current histological evidence of acute rejection (n = 17, p = NS vs. normal subjects). The magnitude of cyclic variation of IB in the septum was 4.8 +/- 1.1 dB in normal subjects and 3.8 +/- 2.0 dB in the cardiac allograft recipients (n = 15, p = NS vs. normal subjects). A significant decrease in the septal IB measure was observed in cardiac allograft recipients with left ventricular hypertrophy (wall thickness of at least 13 mm) (2.6 +/- 1.7 dB, n = 8, p less than 0.05 vs. normal subjects). IB studies were done before and during moderate acute rejection in 11 recipients (14 episodes). During moderate acute cardiac rejection, the magnitude of the cyclic variation in IB decreased from 6.7 +/- 1.3 to 5.1 +/- 1.4 dB in the posterior wall (n = 14, p less than 0.05) and from 4.2 +/- 2.1 dB to 2.9 +/- 1.8 dB in the septum (n = 12, p less than 0.05). These data suggest 1) the magnitude of the cyclic variation in IB of the septum is different in cardiac allografts with cardiac hypertrophy and normal subjects, possibly reflecting regionally depressed myocardial contractile performance and 2) acute cardiac rejection in humans is accompanied by an alteration in the acoustic properties of the myocardium. This change is detectable by serial measurement of the magnitude of the cyclic variation in IB, both in the septum and in the posterior wall.     

Reperfusion arrhythmias after chronic regional denervation of the ischaemic myocardium in pigs.

OBJECTIVE: The aim was to assess the effects of chronic regional denervation of the ischaemic myocardium on reperfusion arrhythmias in a model with sparse coronary collateral circulation. METHODS: Baseline ventricular refractoriness and epicardial activation times were measured together with reperfusion arrhythmias after 15 min (I-15') or 30 min (I-30') of left anterior descending coronary artery occlusion in 38 barbiturate anaesthetised open chest pigs. Twenty pigs (11 in I-15' and nine in I-30') had a chronic (two week) denervation of the left anteroseptal region, whereas 18 pigs (10 in I-15' and eight in I-30') were sham operated (non-denervated) controls. Denervation was induced by pericoronary application of phenol and verified by absence of adrenergic histofluorescence. RESULTS: As compared with controls, denervated pigs showed: (1) longer activation times: 20.3 (SD 5.2) ms v 16.5 (4.6) ms, p < 0.001; (2) slightly longer refractory periods: 348(28) ms v 334(27) ms; (3) a tendency to lower postreperfusion ectopic activity: ectopic beats divided by time free of ventricular tachycardia: 0.13(0.19) v 0.34(0.40) in I-15', and 0.21(0.24) v 0.39(0.44) in I-30'; (4) slower ventricular tachycardia in I-30': 140(29) beats.min-1 v 185(29) beats.min-1, p < 0.009; and (5) comparable incidence of postreperfusion ventricular fibrillation: 4/11 pigs v 2/10 in I-15', and 5/9 v 4/8 in I-30'. CONCLUSIONS: Selective chronic denervation of the ischaemic myocardium was unable to protect against malignant reperfusion arrhythmias in hearts with human-like coronary collaterals. This was confirmed at two ischaemic periods known to produce progressive catecholamine accumulation and increased adrenoceptor density in the ischaemic myocardium.