Coronary collateral stimulation by exercise in dogs with stenotic coronary arteries

1982 ◽  
Vol 52 (3) ◽  
pp. 664-671 ◽  
Author(s):  
M. V. Cohen ◽  
T. Yipintsoi ◽  
J. Scheuer

To determine the effects of an exercise-training program on coronary collateral development, we instrumented 13 1-yr-old beagles with left circumflex (LCf) coronary artery flow probes and balloon occluders and left atrial and aortic catheters. The LCf artery was constricted resulting in a 58 +/- 4% reduction of the peak reactive hyperemia response following release of a 154-s LCf occlusion. All dogs were studied during the first week of the study protocol. Resting heart rate, cardiac output, and left atrial and aortic pressures were evaluated before and during a 1-min LCf occlusion. Myocardial blood flow was also measured with radioactively-labeled microspheres injected into the left atrium during the LCf occlusion. Subsequently the dogs were exercised at 6.4 km/h and 12% grade, and all hemodynamic and blood flow measurements were repeated. The animals were then randomized to either a sedentary or exercising group. The six sedentary animals were confined to their cages, while the seven training beagles did sprint and endurance running for 75 min/day, 5 days/wk. After 12 wk the hemodynamic and blood flow studies were repeated at rest and during treadmill running. There were no statistically significant differences in resting or exercise hemodynamics, response to LCf occlusion, or myocardial blood flow in the two groups in wk 1. Hemodynamics and blood flow data were virtually unchanged in the sedentary animals after 12 wk. However, the trained dogs demonstrated less evidence of left ventricular failure following LCf occlusion while running and had significantly higher myocardial blood flows. Their resting collateral flow increased from 0.52 +/- 0.16 ml . min-1 . g-1 at wk 1 to 0.90 +/- 0.28 ml . min-1 . g-1 at wk 12 (P less than 0.05), while the ratio of collateral to normal myocardial blood flow increased from 0.46 +/- 0.12 to 0.64 +/- 0.16 (P less than 0.05). Thus chronic exercise can stimulate coronary collateral development, and the enhanced collateral flow has a salutary functional effect.

1979 ◽  
Vol 237 (4) ◽  
pp. H520-H527
Author(s):  
M. V. Cohen ◽  
T. Yipintsoi

Fourteen dogs with prior constriction of the left circumflex (LCf) coronary artery were studied at rest and during treadmill running. Hemodynamics were measured before and after a 1-min LCf occlusion. Coronary and collateral flows were quantitated during occlusion both at rest and during exercise. Group I consisted of 4 dogs with resting collateral flow exceeding one-half (average 78%) of normal flow, and group II consisted of 10 dogs with collateral flows less than one-half (average 30%) of normal. At rest LCf occlusion caused no hemodynamic changes in group I, but stroke volume fell significantly in group II. During running, collateral flow after LCf occlusion doubled in group I, and there was only a small rise in left atrial pressure to 18 mmHg. In group II, collateral flow increased by 50% during running and actually decreased in 4 dogs. Significant cardiac failure developed as stroke volume halved, and left atrial pressure rose to an average 30 mmHg. Therefore exercise-induced depression of left ventricular function in the ischemic heart can be correlated to the amount of coronary collateral flow.


1978 ◽  
Vol 45 (5) ◽  
pp. 797-805 ◽  
Author(s):  
M. V. Cohen ◽  
T. Yipintsoi ◽  
A. Malhotra ◽  
S. Penpargkul ◽  
J. Scheuer

To determine the effects of chronic exercise on the coronary collateral circulation of dogs with normal coronary arteries, 1-yr-old purebred beagles were divided into sedentary control and exercising groups. The latter were trained to run on a treadmill. A lower maximal heart rate during a standardized exercise test protocol after a 10- to 12-week training period and a higher gastrocnemius cytochrome oxidase activity in the runners attested to the presence of cardiovascular and skeletal muscle training effects. However, left ventricular weights, left ventricle/body weight ratios, myocardial myofibrillar and myosin ATPases, and hemodynamics were similar in sedentary and exercising dogs except for a significantly higher resting cardiac output in the runners. After occlusion of the left anterior descending coronary artery, both collateral conductance (retrograde flow/aortic pressure) and collateral flow measured with microspheres tended to be lower in the trained dogs, but differences were not significant. The endocardial/epicardial flow ratio in the ischemic area after coronary occlusion did not distinguish between exercisers and controls. Thus treadmill running in the dog with normal coronary arteries produced a training effect, but had no effect on coronary collateral vessels.


1978 ◽  
Vol 234 (6) ◽  
pp. H653-H659 ◽  
Author(s):  
G. R. Heyndrickx ◽  
H. Baig ◽  
P. Nellens ◽  
I. Leusen ◽  
M. C. Fishbein ◽  
...  

The effects of a 15-min coronary occlusion and subsequent reperfusion were investigated in conscious dogs previously instrumented for measurement of left ventricular pressure, dP/dt, regional wall thickening, electrograms, and myocardial blood flow. Coronary occlussion reduced overall left ventricular function only slightly but eliminated systolic wall thickening in the ischemic zone and reduced regional myocardial blood flow in the ischemic zone from 1.04 +/- 0.04 to 0.27 +/- 0.02 ml/min per g and the endo/epi flow ratio from 1.23 +/- 0.04 to 0.44 +/- 0.04, while S-T segment elevation increased from 1.1 +/- 0.3 to 8.2 +/- 0.9 mV. After release of the occlusion, S-T segment elevation disappeared within 1 min while reactive hyperemia in the previously occluded artery and a transient increase in cardiac diastolic wall thickness occurred and then subsided by 15 min. In contrast, systolic wall thickening and the endo/epi flow ratio remained significantly depressed for more than 3 h. Thus reperfusion after a 15 minute coronary occlusion results in a prolonged period of reduced regional myocardial blood flow, particularly in the endocardial layers, which correlates with the prolonged depression of regional myocardial shortening and wall thickening.


1993 ◽  
Vol 264 (3) ◽  
pp. H938-H945
Author(s):  
J. W. Gratama ◽  
J. J. Meuzelaar ◽  
M. Dalinghaus ◽  
J. H. Koers ◽  
A. M. Gerding ◽  
...  

To determine how much myocardial O2 consumption (VO2) would increase during an additional load on the heart in shunt as compared with control lambs, we studied 12 7-wk-old lambs with an aortopulmonary left-to-right shunt (59 +/- 3% of left ventricular output, mean +/- SE) and 11 control lambs during exercise at 80% of their predetermined peak VO2 (VO2peak), at 12 +/- 1 days after surgery. During exercise, systolic aortic pressure increased by 25% in the two groups. Left atrial pressure and left ventricular stroke volume did not change significantly and remained considerably higher in shunt than in control lambs. Heart rate, however, increased less in shunt than in control lambs (163 +/- 8 to 235 +/- 8 vs. 107 +/- 7 to 230 +/- 8 beats/min). The same was true for left ventricular myocardial blood flow (245 +/- 19 to 391 +/- 27 vs. 128 +/- 10 to 320 +/- 45 ml.min-1 x 100 g-1) and myocardial VO2 (847 +/- 101 to 1,692 +/- 136 vs. 528 +/- 58 to 1,579 +/- 178 mumol O2 x min-1 x 100 g-1). We conclude that, despite the volume load, myocardial VO2 of shunt lambs does not increase to a greater extent than in control lambs during a considerable additional load on the heart.


1983 ◽  
Vol 244 (1) ◽  
pp. H23-H31 ◽  
Author(s):  
R. E. Patterson ◽  
E. S. Kirk

The purpose of this study was to compare coronary collateral structure and function in pigs with those in dogs and to analyze the distribution of collateral blood flow across the lateral and transmural border zones in the pig. After acute occlusion of the left anterior descending coronary artery (LAD) in 26 anesthetized open-chest pigs, minimal collateral blood flow was indicated by retrograde flow (0.2 +/- 0.1 ml/min) and microsphere-myocardial blood flow (0.005 +/- 0.001 ml X min-1g-1). Postmortem injection of the distal LAD followed by clearance of the heart demonstrated few tiny collateral structures and negligible collateral filling of other arteries. In contrast to dogs, pigs showed no measurable gradient of collateral blood flow across the transmural border zone, and pigs showed no change in collateral blood flow or its transmural distribution during retrograde drainage of collateral blood flow or elevated left ventricular filling pressures. Pigs showed higher myocardial blood flow in the lateral border than in the center of the ischemic zone. As in the dog, however, this gradient of blood flow across the lateral border zone was accounted for by overlap between occluded LAD branches and unoccluded coronary arterial branches rather than by preferential collateral perfusion of the lateral border of the ischemic zone. We conclude that the pig has a homogeneous distribution of collateral blood flow across the transmural and lateral border zones after acute coronary occlusion but that the minimal collateral circulation limits the usefulness of the pig as a model of ischemic heart disease.


2000 ◽  
Vol 279 (5) ◽  
pp. H2319-H2325 ◽  
Author(s):  
Yingjie Chen ◽  
Ruisheng Du ◽  
Jay H. Traverse ◽  
Robert J. Bache

Sildenafil, a selective inhibitor of phosphodiesterase type 5, produces relaxation of isolated epicardial coronary artery segments by causing accumulation of cGMP. Because shear-induced nitric oxide-dependent vasodilation is mediated by cGMP, this study was performed to determine whether sildenafil would augment the coronary resistance vessel dilation that occurs during the high-flow states of exercise or reactive hyperemia. In chronically instrumented dogs, sildenafil (2 mg/kg per os) augmented the vasodilator response to acetylcholine, with a leftward shift of the dose-response curve relating coronary flow to acetylcholine dose. Sildenafil caused a 6.7 ± 2.1 mmHg decrease of mean aortic pressure, which was similar at rest and during treadmill exercise ( P < 0.05), with no change of heart rate, left ventricular (LV) systolic pressure, or LV maximal first time derivative of LV pressure. Sildenafil tended to increase myocardial blood flow at rest and during exercise (mean increase = 14 ± 3%; P < 0.05 by ANOVA), but this was associated with a significant decrease in hemoglobin, so that the relationship between myocardial oxygen consumption and oxygen delivery to the myocardium (myocardial blood flow × arterial O2 content) was unchanged. Furthermore, sildenafil did not alter coronary venous Po 2, indicating that the coupling between myocardial blood flow and myocardial oxygen demands was not altered. In addition, sildenafil did not alter the peak coronary flow rate, debt repayment, or duration of reactive hyperemia that followed a 10-s coronary occlusion. The findings suggest that cGMP-mediated resistance vessel dilation contributes little to the increase in myocardial flow that occurs during exercise or reactive hyperemia.


1988 ◽  
Vol 254 (2) ◽  
pp. H344-H353 ◽  
Author(s):  
D. Franzen ◽  
R. S. Conway ◽  
H. Zhang ◽  
E. H. Sonnenblick ◽  
C. Eng

Spatial variation (heterogeneity) of myocardial blood flow was studied under basal conditions in relation to four biochemical markers: creatine kinase (CK), lactate dehydrogenase (LDH), ATP, and glycogen. A total of 508 individual 0.5-g samples from the left ventricular free wall was studied in 12 dogs. Myocardial blood flow was measured by radioactive microspheres (15 micron diam) injected via a pigtail catheter into the left ventricle during light sedation (closed-chest flow measurements); following thoracotomy, a second set of microspheres was injected via a catheter into the left atrium (open-chest flow measurements, n = 5). In 27-54 samples/heart, myocardial blood flow, CK, LDH, protein, ATP, and glycogen were determined, permitting a direct correspondence between local blood flow and metabolic markers in each sample and an assessment of the spatial heterogeneity of flow and metabolite content. Correlations between myocardial blood flow per gram tissue and metabolite concentration per gram tissue in pooled data were weak but significant: partial correlation coefficients were 0.137 for CK (P = 0.024), 0.167 for LDH (P = 0.006), 0.341 for ATP (P less than 0.001), 0.123 for glycogen (P = 0.053), but not significant for protein vs. myocardial blood flow. The coefficient of variation, which defines the extent of spatial heterogeneity, averaged 20% for closed-chest flow measurements, 19% for open-chest flow measurements, 22% for CK, 17% for LDH, 15% for protein, 8% for ATP, and 18% for glycogen; these values are over and above the variability due to the technique error, indicating a definite physiological spatial variability. The correlation between local blood flow and the studied metabolites can only explain a minor portion of the spatial heterogeneity of myocardial blood flow. Although a physiological link between blood flow and metabolite content for small regions of the heart is demonstrated, the true local variability of blood flow may be modulated predominantly by other factors.


2001 ◽  
Vol 40 (05) ◽  
pp. 164-171 ◽  
Author(s):  
B. Nowak ◽  
H.-J. Kaiser ◽  
S. Block ◽  
K.-C. Koch ◽  
J. vom Dahl ◽  
...  

Summary Aim: In the present study a new approach has been developed for comparative quantification of absolute myocardial blood flow (MBF), myocardial perfusion, and myocardial metabolism in short-axis slices. Methods: 42 patients with severe CAD, referred for myocardial viability diagnostics, were studied consecutively with 0-15-H2O PET (H2O-PET) (twice), Tc-99m-Tetrofosmin 5PECT (TT-SPECT) and F-18-FDG PET (FDG-PET). All dato sets were reconstructed using attenuation correction and reoriented into short axis slices. Each heart was divided into three representative slices (base, rnidventricular, apex) and 18 ROIs were defined on the FDG PET images and transferred to the corresponding H2O-PET and TT-SPECT slices. TT-SPECT and FDG-PET data were normalized to the ROI showing maximum perfusion. MBF was calculated for all left-ventricular ROIs using a single-compartment-model fitting the dynamic H2O-PET studies. Microsphere equivalent MBF (MBF_micr) was calculated by multiplying MBF and tissue-fraction, a parameter which was obtained by fitting the dynamic H2O-PET studies. To reduce influence of viability only well perfused areas (>70% TT-SPECT) were used for comparative quantification. Results: First and second mean global MBF values were 0.85 ml × min-1 × g-1 and 0.84 ml × min-1 × g1, respectively, with a repeatability coefficient of 0.30 ml ÷ min-1 × gl. After sectorization mean MBF_micr was between 0.58 ml × min1 ÷ ml"1 and 0.68 ml × min-1 × ml"1 in well perfused areas. Corresponding TT-SPECT values ranged from 83 % to 91 %, and FDG-PET values from 91 % to 103%. All procedures yielded higher values for the lateral than the septal regions. Conclusion: Comparative quantification of MBF, MBF_micr, TT-SPECT perfusion and FDG-PET metabolism can be done with the introduced method in short axis slices. The obtained values agree well with experimentally validated values of MBF and MBF_micr.


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