A canine model of chronic ischemic cardiomyopathy: characterization of regional flow-function relations

Firoozan, Soroosh; Wei, Kevin; Linka, André; Skyba, Danny M.; Goodman, Norman C.; Kaul, Sànjiv

doi:10.1016/s0735-1097(98)81755-5

Cited by 17 publications

(23 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although our analysis is limited by the paucity of functional data from chronically dysfunctional myocardium, the data support the notion that there is some degree of flow-function matching in chronic hibernating myocardium because resting flow in chronic stunning would be normal. This finding is consistent with the matched reductions in flow and wall thickening in viable dysfunctional myocardium found among some, but not all, regions of ameroidinstrumented dogs (19) and preliminary studies from our laboratory in pigs with hibernating myocardium from a single LAD stenosis (24). It is interesting to note that the majority of the individual data points show a greater reduction in regional function than the reduction in relative flow.…”

supporting

confidence: 87%

“…Some investigators have suggested that regional dysfunction is disproportionately depressed relative to the modest reductions in flow in regions of hibernating myocardium (8). Others have suggested heterogeneity of mechanisms when myocardial flow and function are analyzed on a segmental basis, with chronic stunning and hibernating myocardium being present in the same heart (19,33). Our results with direct microsphere measurements indicate that flow is chronically reduced in hibernating LAD myocardium compared with normal remote regions as well as sham controls.…”

mentioning

confidence: 47%

“…This heterogeneity most likely reflected variability among animals with regard to the stenosis severity and its physiological effects on subendocardial flow during vasodilation. Firoozan et al (19) produced globally reduced LV function in dogs instrumented with up to four ameroid occluders. Although there was evidence of progressive LV dilatation in this model, there were no sham controls for comparison.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Ischemic cardiomyopathy in pigs with two-vessel occlusion and viable, chronically dysfunctional myocardium

Fallavollita

Canty

2002

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Fallavollita, James A. and John M. Canty, Jr. Ischemic cardiomyopathy in pigs with two-vessel occlusion and viable, chronically dysfunctional myocardium. Am J Physiol Heart Circ Physiol 282: H1370-H1379, 2002; 10.1152/ajpheart.00138.2001.-A chronic left anterior descending coronary artery (LAD) stenosis leads to the development of hibernating myocardium with severe regional hypokinesis but normal global ventricular function after 3 mo. We hypothesized that two-vessel occlusion would accelerate the progression to hibernating myocardium and lead to global left ventricular (LV) dysfunction and heart failure. Pigs were instrumented with a fixed 1.5-mm constrictor on the proximal LAD and circumflex arteries. After 2 mo, there were no overt signs of right-heart failure and triphenyl tetrazolium chloride infarction was trivial (1.4 Ϯ 0.1% of the LV). Compared with shams, regional function [myocardial systolic excursion (⌬WT); 2.1 Ϯ 0.3 vs. 4.6 Ϯ 0.4 mm, P Ͻ 0.05] and resting perfusion (0.90 Ϯ 0.13 vs. 1.32 Ϯ 0.09 ml ⅐ min Ϫ1 ⅐ g Ϫ1 , P Ͻ 0.05) were reduced, consistent with hibernating myocardium. Pulmonary systolic (45.9 Ϯ 3.3 vs. 36.5 Ϯ 2.2 mmHg, P Ͻ 0.05) and wedge pressures (19.1 Ϯ 1.6 vs. 11.2 Ϯ 0.9 mmHg, P Ͻ 0.05) were increased with global ventricular dysfunction (ejection fraction 43 Ϯ 2 vs. 50 Ϯ 2%, P Ͻ 0.05). Early LV remodeling was present with increased cavity size and mass. Reductions in sarcoplasmic reticulum Ca 2ϩ -ATPase and phospholamban were confined to the dysfunctional LAD region with no change in calsequestrin. Thus combined stenoses of the LAD and circumflex arteries accelerate the development of hibernating myocardium and result in compensated heart failure. hibernating myocardium; stunned myocardium; pigs; collaterals; heart failure; ischemic cardiomyopathy ISCHEMIC CARDIOMYOPATHY is an increasingly prevalent cause of death and disability from cardiovascular disease (20). Unfortunately, major deficiencies exist in our understanding of how chronic coronary artery disease progresses to symptomatic left ventricular (LV) dysfunction due to the lack of experimental animal models where the progression of physiological, cellular, and molecular responses can be evaluated longitudinally. Although some patients develop heart failure due to muscle loss and replacement fibrosis in association with large or multiple myocardial infarcts (1, 6, 29), pathological studies support the view that many patients have global LV dysfunction, disproportionately severe in relationship to the amount of replacement fibrosis identified at postmortem exam (3, 31). Two of the factors that could contribute to this dissociation include a chronic depression in myocyte contractile function due to alterations in sarcoplasmic reticulum (SR) function and LV remodeling with diffuse interstitial connective tissue proliferation and myocyte cell dropout due to apoptosis (28). An additional explanation for the dissociation between the severity of LV dysfunction and fixed structural changes could be reversible contractile dysfunction arisi...

show abstract

supporting

confidence: 87%

mentioning

confidence: 47%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ischemic cardiomyopathy in pigs with two-vessel occlusion and viable, chronically dysfunctional myocardium

Fallavollita

Canty

2002

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…13,14 Dogs were heavily sedated with 20 mg/kg fentanyl and 300 mg/kg etomidate. Dogs were placed on their left side, paralyzed with 300 g/kg atracurium, intubated, and ventilated with room air by means of a respirator pump.…”

Section: Experimental Protocolmentioning

confidence: 99%

Mechanism of Inducible Regional Dysfunction During Dipyridamole Stress

Bin

Pelberg

et al. 2002

Circulation

View full text Add to dashboard Cite

Background-We hypothesized that increased myocardial oxygen demand resulting from hypotension and reflex tachycardia unmasking a reduced endocardial myocardial blood flow (MBF) reserve is the mechanism of dipyridamole-induced regional dysfunction in chronic coronary artery disease. Methods and Results-Ameroid constrictors were placed around the proximal coronary arteries and their major branches in 15 dogs to create chronic coronary stenosis. Seven days later, radiolabeled microsphere-derived MBF and 2-dimensional echocardiography-derived percent wall thickening (%WT) were measured at rest and after 0.56 mg/kg dipyridamole. Dipyridamole caused an increase (mean, 21%) in the rate-pressure product secondary to reflex tachycardia resulting from mild systemic hypotension. %WT in myocardial segments with an endocardial MBF reserve (dipyridamole/resting MBF) of 1.5 to 2.5 (nϭ35) did not change after dipyridamole, whereas it decreased in segments with an endocardial MBF reserve of Ͻ1.5 (nϭ30) and increased in those with an endocardial MBF reserve of Ն2.5 (nϭ45) (PϽ0.05). Most (80%) segments with endocardial MBF reserve of Ͻ1.5 and 14% with an endocardial MBF reserve of 1.5 to 2.5 showed inducible dysfunction after dipyridamole, whereas none of the segments with an endocardial MBF reserve of Ն2.

show abstract

“…We hypothesized that cardiac denervation caused by TMR would lead to attenuation of paradoxical vasoconstriction, thus ameliorating ischemia, which would explain the angina relief and improved exercise tolerance seen in patients undergoing this procedure. We tested our hypothesis in a canine model of chronic ischemic cardiomyopathy previously developed by us 29,30 .…”

Section: Introductionmentioning

confidence: 99%

Transmyocardial revascularization ameliorates ischemia by attenuating paradoxical catecholamine-induced vasoconstriction

Powers

Bin

et al. 2007

Journal of Nuclear Cardiology

View full text Add to dashboard Cite

The mechanism by which transmyocardial revascularization (TMR) offers clinical benefit is controversial. We hypothesized that TMR ameliorates ischemia by reversing paradoxical catecholamine-induced vasoconstriction. Chronic ischemic cardiomyopathy was created in 11 dogs by placing ameroid constrictors on the proximal coronary arteries and their major branches. Six weeks later, 35 channels were created percutaneously in the left circumflex artery (LCx) region with the left anterior descending artery (LAD) region serving as control. At rest, wall thickening (WT) and myocardial blood flow (MBF) did not change in the treated region, while they deteriorated in the control bed. Contractile and MBF reserve increased in the treated region but deteriorated in the control region. There was diminished 123 I-metaiodobenzylguanidine uptake and significant reduction in noradrenergic nerves in the treated region compared to control region, with corresponding reduction in tissue tyrosine hydroxylase activity. We conclude that the absence of catecholamine-induced reduction in MBF reserve and contractile reserve in the TMR treated region with associated evidence of neuronal injury indicates that the relief of exercise-induced ischemia after TMR is most likely due to reversal of paradoxical catecholamine-induced vasoconstriction. These findings may have implications in selecting patients who would benefit from TMR.

show abstract

A canine model of chronic ischemic cardiomyopathy: characterization of regional flow-function relations

Cited by 17 publications

References 0 publications

Ischemic cardiomyopathy in pigs with two-vessel occlusion and viable, chronically dysfunctional myocardium

Ischemic cardiomyopathy in pigs with two-vessel occlusion and viable, chronically dysfunctional myocardium

Mechanism of Inducible Regional Dysfunction During Dipyridamole Stress

Transmyocardial revascularization ameliorates ischemia by attenuating paradoxical catecholamine-induced vasoconstriction

Contact Info

Product

Resources

About