To investigate the electrocardiographic and hemodynamic changes in isolated right ventricular infarction, 0.25 ml or 0.5 ml of metallic mercury was injected into the right coronary artery of 14 closedchest dogs. At autopsy, at least 60% of the right ventricle was necrotic in every dog. Heniodynamic observations were made in 11 and electrocardiographic mapping was performed in all 14 dogs. Right atrial pressure rose in 10 and left atrial pressure in nine of the 11 dogs; early right atrial pressure did not exceed left atrial pressure, but late right atrial pressure was greater in four dogs. Although cardiac output and blood pressure fell significantly, circulation was maintained. Twelve of 14 dogs had transient ST-segment elevation in the right precordial leads, and 12 developed right bundle branch block. Abnormal Q waves or R waves of 1 mm or less appeared in the right precordial leads in 13 of the 14 dogs. Since right bundle branch block and abnormal Q waves in the right precordial leads have not been recognized as useful signs in human right ventricular infarction, further investigations are warranted to determine their value in clinical applications.

Myocardial uptake and washout of thallium-201 (20TI) were studied in an experimental dog model in which regional blood flow to the posterior wall was varied by transient 2-minute occlusion of the circumflex coronary artery to produce transient ischemia and reactive hyperemia. Thallium-201 myocardial activity in a region of interest was determined continuously after i.v. administration by a gamma camera and computer program. Activity in the posterior wall was compared with that in the anterior wall in the same dog and the posterior wall of control dogs. Thallium-201 uptake was directly related to blood flow. With reactive hyperemia, there was a rapid and absolute increase in uptake followed by rapid washout; with ischemia, there was slow and decreased uptake followed by a slow washout. The calculated myocardial activity during washout in both ischemic and hyperemic areas approached values in control dogs long after blood flow had returned to baseline levels. Significant differences in washout slopes were found between the three groups of dogs (-0.156%/min in control dogs, -0.244%/min after reactive hyperemia, and -0.076%/min after transient ischemia, with half-washout times of 5.3 hours, 3.4 hours and 11.0 hours, respectively). These data suggest that both the initial decrease in activity in the ischemic area and the initial excess in the hyperemic area are corrected by different washout rates of ischemic and hyperemic cells during redistribution.

Background. Although recent studies suggest that pulmonary venous flow velocities may be used to evaluate left ventricular diastolic function, the influence of loading conditions and contractile state on the magnitude and pattern of pulmonary venous flow are poorly understood. Methods and Results. Fourteen anesthetized open-chest mongrel dogs were instrumented with pulmonary venous flow probes, atrial sonomicrometer crystal pairs, and high-fidelity micromanometers; transesophageal Doppler echocardiography was used to obtain simultaneous pulmonary venous flow velocities. Measurements were made over a wide range of left atrial pressure obtained by either intravascular volume infusion and inferior vena caval balloon inflation (n=8), halothane inhalation (n=6), or phenylephrine infusion (n=5). There was an excellent correlation for pulmonary venous systolic (J) to diastolic (K) time integral between the Doppler and flow probe signal (r=0.94; SEE, 0.18). When left atrial pressure was increased by volume infusion, there was a significant linear relation between mean left atrial pressure and the Doppler J/K peak (r=0.64; SEE, 3.4 mm Hg) and flow velocity-time integral ratio (r=0.75; SEE, 2.9

Background I'Tc-Q12 is a new Tc(III) perfusion imaging agent that permits prompt myocardial visualization in humans. We postulated that 9'Tc-Q12 myocardial activity is related to actual myocardial blood flow during conditions of myocardial ischemia and pharmacological coronary artery vasodilation and that 99'Tc-Q12 shows little or no myocardial redistribution as long as 4 hours after intravenous injection. Methods and Results In seven anesthetized, open chest dogs, the left circumflex coronary artery was occluded, and dipyridamole (0.32 or 0.56 mg/kg) was infused into the right atrium, followed by 10 mCi of 'Tc-Q12. Myocardial blood flow was measured by radiolabeled microspheres. The animals were euthanized, and a total of 315 myocardial samples were assayed in a well counter for 9'Tc activity. One week later, radiolabeled microsphere activity was determined, and myocardial blood flow was calculated. 9'9Tc activity (y) was related to myocardial blood flow (x) from 0 to 2 mL* g` . min-' by the relation y=0.64x+0.35 (r=.88, P=.0001). In 14 additional anesthetized, open chest dogs, an occluder was placed around the left circumflex coronary artery, and an ischemic level of circumflex blood flow was maintained constant over 4 hours as measured by an ultrasonic flowmeter. Dipyridamole (0.56

Rapid atrial pacing produces atrial systolic and diastolic failure characterized by absent atrial booster pump function, increased atrial chamber stiffness, enhanced atrial conduit function, and atrial enlargement. However, the processes underlying these abnormalities are poorly understood. Therefore, we examined left atrial myocardium from dogs with rapid pacing-induced atrial failure (400 bpm for 6 weeks) and from control dogs. Western blotting was used to determine the levels of proteins involved in calcium homeostasis (SERCA 2A, phospholamban, Na + -Ca 2+ exchanger). Matrix metalloproteinase (MMP) activity was measured using gelatin and casein zymography, and levels of tissue inhibitor of metalloproteinase-4 (TIMP-4) and the TIMP-4 complexed with MMPs were measured with Western blot analysis. There were no differences in SERCA 2A or Na + -Ca 2+ exchanger protein levels, but phospholamban level was significantly decreased in atrial samples from rapidly paced dogs (51.2 ± 7.8 vs. 77.0 ± 10.0, p < 0.01). The activity of MMP-9 was selectively and significantly increased by ∼ 50%, and the level of complexed TIMP-4 protein was significantly decreased by ∼ 50% in samples from dogs with atrial failure. Thus, rapid pacing-induced atrial failure is associated with differential changes in MMP activity, an unchanged number of calcium pumps, and compensatory changes in the level of phospholamban.

In immature animals, effects of pacing-induced heart failure on systolic and diastolic properties and associated changes in Ca2+ handling proteins of the cardiocyte have not been studied. We utilized force-frequency(FFR) and relaxation-frequency relationships (RFR), which reflect changes in Ca2+ cycling by sarcoplasmic reticulum (SR) & sarcolemma (SL). We studied 6 young goats (Age: 4 wks), paced at 300 bpm for a period 2.5 weeks prior to the experiment (P group) and 5 age matched controls (C group). LV dP/dtmax and time constant of relaxation (τ) were calculated from LV micromanometric tracings at increasing heart rates (HR) generated by right atrial pacing after infusing a sinus node blocker. HR at which pulsus alternans appeared was defined as “Critical HR” (HRcrit). Parameters were remeasured after ryanodine, a SR Ca2+ channel release blocker (5 μg/kg). Table

The objective of this study was to examine the hypothesis that long-term, rapid atrial pacing produces a model of atrial systolic and diastolic dysfunction but does not alter ventricular function. Eight dogs were atrially paced at 400 beats/min (3:1-5:1 ventricular response) for 6 wk and subsequently instrumented with left atrial (LA) and left ventricular (LV) sonomicrometers and micromanometers. Data were compared with those from six sham-operated controls at matched heart rates and mean LA pressures of 10 mmHg. Dogs with rapid pacing had slightly greater LA volume (10.3 +/- 4.0 vs. 7.9 +/- 4.4 ml) and reduced ejection fraction (2.2 +/- 1.4 vs. 13.0 +/- 4.0, P < 0.05), systolic ejection rate (0.3 +/- 0.1 vs. 2.8 +/- 1.2 vol/s, P < 0.05), and reservoir fraction (0.07 +/- 0.04 vs. 0.35 +/- 0.06, P < 0.05) compared with controls. LA diastolic chamber stiffness was greater after rapid atrial pacing than before (stiffness constant k(c), 5.7 +/- 2.3 vs. 3.4 +/- 0.6, P < 0.05), and the ratio of transesophageal echo-determined pulmonary venous systolic to diastolic integrated flow (a measure of relative reservoir to conduit function of the LA) was less in rapidly paced dogs compared with control dogs (0.41 +/- 0.19 vs. 0.68 +/- 0.23, P < 0.05). In contrast, rapid atrial pacing did not influence LV systolic performance or lusitropy, because the LV pressure time derivative and the time constant of LV relaxation were similar in both groups. In this model of isolated atrial myopathy, increased atrial stiffness and enhanced conduit function compensate for impaired atrial booster pump and reservoir functions.

A recent investigation revealed that triphenyl tetrazolium chloride (TTC) staining had a significant effect on myocardial uptake determinations of radiolabeled tracers with experimental infarction/reperfusion studies. We therefore investigated the impact of TTC staining on technetium-99m-Q12 and thallium-201 myocardial uptake in canines during infarction. Ten adult male mongrel dogs underwent a left anterior descending occlusion for 2 hours and subsequent injection of Q12 or thallium with 30 minutes of circulation. The whole heart was then excised, washed with saline, and myocardial counts were determined by a well counter. The heart was then perfused with 1% TTC stain for 5–10 minutes and then recounted.

An accurate noninvasive method for measuring the effects of pharmacologic agents on active relaxation of the left ventricle would provide a valuable tool for monitoring the treatment of diastolic heart failure related to coronary artery disease.

Antiarrhythmic drugs can interfere with electrical defibrillation using monophasic non-sequential shocks (MS). It is unknown if these drugs affect the efficacy of biphasic defibrillation shocks (BS). Since MS and BS waveforms can exhibit disparate effects on myocardial excitability and refractoriness (properties which may influence defibrillation efficacy), it is possible that antiarrhythmic drugs, such as lidocaine (L), will affect defibrillation threshold (DFT) of one waveform differently than another. We studied 25 pentobarbital anesthetized farm swine who had endocardial pacing and monophasic action potential catheters placed into the right ventricle. Pacing was used to induced sustained ventricular fibrillation (5-8 s) which was followed by defibrillation via epicardial electrodes. Each pig was assigned to one of four treatment groups; 1) MS + D5W (n = 7), 2) MS + L (n = 7) 3) BS + D5W (n = 5), or 4) BS + L (n = 7). DFTs were measured at baseline (Base) and subsequently during treatment (D5W or L). DFT values (joules) predicting 50% success at baseline were: + D5W = 7.34 ± 1.59, MS + L= 7.11 ± 1.5, BS + D5W = 5.28 ± 1.55 and BS + L = 3.86 ± 1.2. The figure depicts Download : Download high-res image (130KB) Download : Download full-size image treatment DFT values as percent of baseline. In the MS groups, the change in DFT from Base to L was 92 ± 28% vs the change from Base to D5W of 0.6 ± 29% (p l 0.0001). In the BS groups, however, the change in DFT from Base to L was similar to the change from Base to D5W (-6.7 ± 15 vs -29 ± 17%, p = 0.08). Compared to D5W, L increased DFT in the biphasic group by a magnitude that was ¼ that seen in the monophasic group. Clinical Implications: The effect of antiarrhythmic drugs on DFT (especially increased DFT values) may be less of a concern when using implantable devices employing biphasic waveforms.