Biomedical subjects

L Hittinger

Publications and source records attributed to L Hittinger.

At least 37 records · Page 2Linked to original sources

PubMed1999

Comparison between angiotensin receptor antagonism and converting enzyme inhibition in heart failure. Differential acute effects according to the renin-angiotensin system activation.

This study was designed to assess the influence of the activation status of the renin angiotensin system (RAS) on the hemodynamic effects of EXP 3174 (an angiotensin AT1 receptor antagonist) and enalaprilat (an angiotensin converting enzyme inhibitor) in tachycardia-induced heart failure. Thirteen dogs were chronically instrumented to measure left ventricular (LV) pressure, its first time derivative (LV dP/dt), atrial and aortic pressures, and cardiac output. EXP 3174 (0.1 mg/kg, i.v.) or enalaprilat (1 mg/kg, i.v.) were administered in conscious dogs with heart failure induced by right ventricular pacing (250 beats/min, 3 weeks). EXP 3174 and enalaprilat produced significant vasodilation but the effects of EXP 3174 on mean aortic pressure (MAP), cardiac output, and total peripheral resistance (TPR) were only 50% of those produced by enalaprilat. When dogs were grouped according to their baseline plasma renin activity (PRA) values, in dogs with normal PRA (0.5 +/- 0.1 ng/ml/h) EXP 3174 did not produce significant change in MAP and TPR, while enalaprilat decreased significantly MAP and TPR. In contrast, in dogs with high PRA (6.7 +/- 3.2 ng/ml/h), EXP 3174 produced significant reductions in MAP and TPR, which were similar to those produced by enalaprilat. Thus, in conscious dogs with heart failure, enalaprilat is effective whether the RAS is activated or not. In contrast, EXP 3174 is effective only when the RAS is activated. These results may help in the choice of inhibitors of the RAS in heart failure.

Angiotensin II↗

PubMed1999

Influence of the endothelium, nitric oxide and serotonergic receptors on coronary vasomotor responses evoked by ergonovine in conscious dogs.

1. The respective contributions of coronary vascular endothelium, nitric oxide (NO) and serotonergic receptors to the effects of ergonovine on large and small coronary arteries were investigated in conscious dogs. 2. In seven dogs with an endothelium intact, ergonovine (30 - 1000 microg, i.v.) induced a biphasic response on large coronary artery with an early and transient vasodilatation (up to +2.9+/-0.5% from 3310+/-160 microm, P<0.01) followed by a sustained vasoconstriction (down to -4.9+/-0.5%, P<0.001) which occurred simultaneously with a sustained increase in coronary blood flow (CBF) (up to +100+/-26% from 28+/-4 ml min(-1), P<0.001). After endothelium removal (balloon angioplasty), the ergonovine-induced vasodilatation was abolished and vasoconstriction potentiated (-6.4+/-0.9% after vs -4.9+/-0.5% before endothelium removal, P<0.01). 3. After blockade of NO synthesis by Nomega-nitro-L-arginine (30 mg kg(-1)) in four other dogs, the early vasodilatation induced by ergonovine was abolished but the delayed vasoconstriction as well as the increase in CBF remained unchanged. 4. Both ketanserin and methiothepin (0.3 mg kg(-1)) abolished the early vasodilatation and reduced the delayed vasoconstriction induced by ergonovine. Ketanserin decreased and methiothepin abolished the reduction in coronary resistance induced by ergonovine. 5. Thus, the complex interactions between vascular endothelium and serotonergic receptors to ergonovine-induced constriction of large coronary arteries might explain the induction of coronary spasms in patients with endothelial dysfunction.

Animals↗

PubMed1999

Increased bradykinin levels accompany the hemodynamic response to acute inhibition of angiotensin-converting enzyme in dogs with heart failure.

To determine the short-term effects of angiotensin-converting enzyme (ACE) inhibition on hemodynamics and circulating levels of norepinephrine, angiotensin, and bradykinin, responses to enalaprilat and perindoprilat were examined at doses of 0.03, 0.3, and 1 mg/kg in permanently instrumented conscious dogs with pacing-induced heart failure (right ventricular pacing, 240-250 beats/min, 3 weeks). All doses of the two inhibitors produced similar decrease in mean aortic pressure and increase in cardiac output. Neither inhibitor affected plasma norepinephrine level. Both compounds induced a similar 60-80% decrease in blood angiotensin II level, a similar two- to eightfold increase in blood angiotensin I level, and a 80-95% decrease in the angiotensin II/angiotensin I ratio. There were also a fourfold to 10-fold increase in blood bradykinin-(1-9) level, a twofold increase in blood bradykinin-(1-7) level, and a 70-85% decrease in bradykinin-(1-7)/bradykinin-(1-9) ratio. In addition, the changes in total peripheral resistance induced by the two ACE inhibitors were weakly but significantly correlated with the changes in blood angiotensin II or blood bradykinin-(1-9). Thus whatever the specificity of enalaprilat and perindoprilat, both inhibitors produced similar acute hemodynamic effects in dogs with heart failure, which was associated with marked decrease in circulating angiotensin II level and increase in bradykinin-(1-9) level. This study, which measures for the first time in heart failure the blood bradykinin level after ACE inhibitors, indicates, in concert with angiotensin II reduction, a role for increased bradykinin-(1-9) level in mediating short-term hemodynamic effects of ACE inhibition in this model of heart failure.

Angiotensin I↗

PubMed1999

[Coronary microcirculation. Physiologic and pathologic aspects].

The coronary circulation has a protective regulation system which, in extreme haemodynamic conditions, compensates increased myocardial oxygen demand. The coronary reserve, based on this concept defines the capacity of the system to increase flow temporally, and, thereby, myocardial oxygen supply. The introduction of new methods of investigating the coronary microcirculation has enabled the study of this phenomenon in several cardiovascular pathologies. Two types of investigation are used currently for studying the coronary microcirculation: 1) invasive methods, especially the recently developed intracoronary Doppler and pressure guide, 2) non-invasive methods, and, in particular, contrast echocardiography, position emission tomography and magnetic nuclear resonance. These investigations allow measurement of the coronary reserve or the assessment of the myocardial consequences of abnormalities of the microcirculation. Some workers use these methods to investigate pathological coronary microcirculation in different cardiomyopathies, in the presence of different cardiovascular risk factors (hypertension, diabetes, smoking, hypercholesterolaemia) and after cardiac transplantation.

Coronary Circulation↗

PubMed1999

Coronary microcirculation and cardiovascular pathology.

The recent arrival of new techniques for exploring the coronary microcirculation has facilitated assessment of both the incidence and consequences of disorders of this network in a large number of cardiovascular diseases. The microcirculation is affected in numerous cardiomyopathies in the presence of different cardiovascular risk factors and also following cardiac transplantation. Dysfunction of the microcirculation may correspond to a reduction in the surface of the maximum section of coronary arterioles, which involves multiple mechanisms, although this phenomenon does not appear to play a role in ischaemic heart disease. Reduced coronary flow is most frequently related to vascular rarefaction of multifactorial origin, including greater or lesser degrees of intimal proliferation, perivascular fibrosis, hypertrophy of the media and extrinsic compression.

Cardiovascular Diseases↗

PubMed1999

Coronary microcirculation and cardiovascular pathology.

Cardiovascular Diseases↗

PubMed1998

Acute effects of an endothelin-1 receptor antagonist bosentan at different stages of heart failure in conscious dogs.

OBJECTIVE: Inhibition by endothelin antagonist is a potential therapy in heart failure. However, the effect of endothelin inhibition during the development of heart failure has not been evaluated. The goal of our study was to examine the acute hemodynamic effects of the mixed endothelin receptor antagonist bosentan in the control state and at different stages of heart failure induced by right ventricular pacing (250 bpm) in conscious dogs. METHODS: Nine dogs were chronically instrumented for the measurements of left ventricular pressure and its first derivative (dP/dt), cardiac output, left ventricular regional wall thickness and aortic pressure. Bosentan (3 mg/kg, i.v. bolus) and placebo were given at control, at 1 week of pacing (stage of left ventricular dysfunction with perserved cardiac output) and at 3 weeks of pacing (phase of heart failure with low cardiac output). RESULTS: With the development of heart failure, baseline plasma endothelin level increased progressively. Placebo did not induce hemodynamic and plasma endothelin changes during the 30 min recording at any stage. At control, bosentan did not change hemodynamics. At 1 and 3 weeks of pacing, bosentan did not modify left ventricular myocardial function indices but reduced mean arterial pressure (by 7 +/- 2 and 8 +/- 1 mm Hg respectively, p < 0.005). Bosentan increased stroke volume at 3 weeks of pacing only. CONCLUSIONS: Endothelin inhibition by endothelin antagonist bosentan, decreases aortic pressure in both early left ventricular dysfunction and in heart failure in contrast with the control state. In the phase of heart failure with low cardiac output, bosentan increases stroke volume. In the early left ventricular dysfunction, bosentan, by reducing arterial pressure, may limit the deterioration of cardiac function through a reduction of the workload imposed on the heart.

Animals↗

PubMed1998

Selective large coronary endothelial dysfunction in conscious dogs with chronic coronary pressure overload.

Coronary vascular responses to acetylcholine (ACh, 3 micrograms/kg i.v.), nitroglycerin (NTG, 25 micrograms/kg i.v.), and a 20-s coronary artery occlusion (reactive hyperemia, RH) were investigated in seven conscious dogs with severe left ventricular (LV) hypertrophy and chronic coronary pressure overload (CCPO) due to supravalvular aortic banding and in seven control dogs. All dogs were instrumented for measurement of ultrasonic coronary diameter (CD) and Doppler coronary blood flow (CBF). LV-to-body weight ratio was increased by 82% in CCPO dogs. In control dogs, ACh increased CD (+ 5.9 +/- 1.7%). This response was reduced (P < 0.05) in CCPO dogs (+ 1.9 +/- 0.9%). Similarly, flow-mediated increases in CD after RH were blunted (P < 0.01) in CCPO (+ 2.1 +/- 0.8) vs. control dogs (+ 6.8 +/- 1.8%). In contrast, ACh and RH increased CBF similarly in both groups. Increases in both CD and CBF to NTG were not different between control dogs and CCPO. Peak systolic CBF velocity was greater, P < 0.01, in CCPO (94 +/- 17 cm/s) compared with control (35 +/- 7 cm/s) dogs, most likely secondary to the increased systolic coronary perfusion pressure (215 vs. 130 mmHg). Histological analyses of large coronary arteries in CCPO revealed medial thickening, intimal thickening, and disruption of the internal elastic lamina and endothelium. In contrast, small intramyocardial arterioles failed to show the intimal and endothelial lesions. Thus, in CCPO selective to the coronary arteries, i.e., a model independent from systemic hypertension and enhanced levels of plasma renin activity, endothelial control was impaired for both flow-mediated and receptor-mediated large coronary artery function, which could be accounted for by the major morphological changes in the large coronary arteries sparing the resistance vessels. The mechanism may involve chronically elevated systolic coronary perfusion pressure, CBF velocity, and potential disruption of laminar flow patterns.

Acetylcholine↗

PubMed1998

[Effects of high sodium intake on ventricular remodeling in mice].

BACKGROUND: Despite extensive research, controversy still exists regarding the role of dietary sodium intake on hypertension and left ventricular (LV) hypertrophy. Echocardiography is a powerful tool to assess LV hypertrophy and recent technical developments allow now its use in small animals. METHODS: We examined the effect of high sodium intake on LV geometry using echocardiography in mice. Three groups of Swiss mice were submitted, for 8 weeks, to different salt diets (0.6, 2 and 4% NaCl; n = 12, n = 8 and n = 12 respectively). LV end-diastolic (ED) septal and posterior wall thicknesses, LV ED diameter were measured at baseline, 4 and 8 weeks. RESULTS: At baseline, heart rate, LV ED septal and posterior wall thicknesses and LV ED diameter were similar between groups. At 8 weeks, for similar heart rate, LV ED posterior wall thickness were not different (0.6%: 0.64 +/- 0.01, 2%: 0.62 +/- 0.08 and 4%: 0.67 +/- 0.03 mm respectively) but LV septal wall thickness ass increased in a salt diet dependent manner (0.6%: 0.63 +/- 0.01, 2%: 0.75 +/- 0.01, 4%: 0.80 +/- 0.02 mm, p < 0.01). This increase was correlated with urinary sodium excretion (r = 0.84, p < 0.01) but occurred in the absence of change in arterial pressure (tail-cuff plethysmography; 0.6%: 135 +/- 6.2%: 127 +/- 4 and 4%: 139 +/- 9 mmHg respectively). The in-vivo interventricular septal remodeling was confirmed in perfused fixed preparations of hearts. CONCLUSION: Echocardiography allows precise measurements of regional LV wall dimensions in mice, and high sodium intake, in the absence of hypertension, induces interventricular septal remodeling.

Animals↗

PubMed1998

[Physiopathological basis of the treatment of heart failure].

Therapeutic advances have changed the mode of presentation of cardiac failure over the last decades: the main cause, nowadays, is myocardial ischaemia. The modern treatment of cardiac failure is based on relatively simple physiopathological mechanisms which take into account the different aspects of cardiac physiology: a pump, a muscle, a coronary circulation supplying oxygen to the myocardium, an automatic contraction. The concept of vasodilatation and the blocking of vasoconstrictive systems introduced during the 70s is the basis of modern treatment of cardiac failure which involves angiotensin converting enzyme inhibitors and, increasingly, betablockers. In the near future, with earlier treatment of cardiac failure, the stimulation of vasodilator systems could become a new therapeutic strategy. Early detection of ischaemia and its complications with the aim of limiting the loss of cardiac myocytes is a priority for slowing the progression of cardiac failure. The prevention of cardiac failure also depends on educating cardiologists to treat rapidly the factors predisposing to or prolonging episodes of even mild cardiac failure.

Cardiology↗

PubMed1997

Regional myocardial effects of intracoronary bradykinin in conscious dogs.

This study examined in conscious dogs, the coronary and regional myocardial effects of bradykinin (BK) administered by intracoronary route and their modulation by an angiotensin-converting enzyme inhibitor. Eleven dogs were chronically instrumented with a left ventricular (LV) micromanometer, a circumflex coronary catheter, a flow probe, and ultrasonic crystals in the LV posterior wall. In the absence of systemic hemodynamic changes, BK (0.1-10 ng/kg i.c.) produced dose-dependent increases in coronary blood flow velocity (CBFV) and in LV posterior end-diastolic wall thickness (EDWT) but produced no change in LV regional myocardial function as assessed by LV posterior systolic wall thickening. The increases in LV EDWT and CBFV were linearly correlated. The BK B2 antagonist (HOE 140) abolished the effects of BK. Intracoronary enalaprilat (0.75 mg) extended the duration of the effect of BK on CBFV without modification of peak responses and induced a further increase in LV posterior EDWT but no change in LV regional myocardial function. Thus, in conscious dogs, the vasodilator effect of intracoronary BK alone or modulated by enalaprilat is not associated with changes in LV regional myocardial function.

Animals↗

PubMed1996

Coronary vascular morphology in pressure-overload left ventricular hypertrophy.

To attempt to explain the loss of subendocardial coronary reserve in chronic pressure-overload cardiac hypertrophy on a morphologic basis, we measured capillary capacity and coronary artery and arteriole medial wall area in dogs with moderately severe chronic (1 year) left ventricular hypertrophy (LVH). Aortic bands were placed on the ascending aorta of 8-10-week-old puppies of either sex, and hearts were perfusion fixed with 2% glutaraldehyde 8-16 months later after hemodynamic study while fully conscious. Left ventricular (LV) mass/body weight ratio in 11 banded dogs with LV end-diastolic pressure < 12 mmHg was 72% greater than in 15 controls (C). There was a decrease in subendocardial coronary reserve during adenosine-induced vasodilation with a shift away from the subendocardium (endo/epi flow ratio: C = 0.68 +/- 0.05; LVH = 0.34 +/- 0.06; P < 0.05). In spite of the extensive hypertrophy, image analysis revealed capillary density to be equally reduced by only 10-15% in endo, mid and epicardial LV regions compared to control dogs, while increased capillary cross-sectional area resulted in no change in capillary surface area/myocyte volume or volume percentage capillary space. In addition to these data suggesting capillary angiogenesis, there was no reduction in arteriolar density, indicating transmural increase in arteriolar number, and, as a consequence, increased total length of the resistance vessels. Medial area of arterioles and arteries showed a graduated increase according to size. We concluded that due to the lack of transmural difference in vascular morphology in chronic (1 year) moderately severe LVH, these anatomic bases do not play a major role as a cause for the loss of coronary reserve. Regional functional differences as a consequence of the morphologic alterations, however, cannot be excluded.

Adenosine↗

PubMed1996

Repeated coronary artery occlusions during routine balloon angioplasty do not induce myocardial preconditioning in humans.

OBJECTIVES: The purpose of the present study was to assess whether brief, repeated coronary artery occlusions during balloon angioplasty induce a myocardial ischemic protective effect. BACKGROUND: In animals, brief coronary artery occlusions preceding a more prolonged occlusion result in reduced infarct size. Whether myocardial protection against ischemia could also occur in humans during angioplasty remains controversial. METHODS: Thirteen patients with a proximal left anterior descending coronary artery stenosis with no angiographic collateral circulation underwent percutaneous transluminal coronary artery balloon angioplasty. Three 120-s balloon inflations separated by a 5-min equilibration period were performed. For each inflation, intracoronary ST segment modifications, septal wall thickening (M-mode echocardiography), left ventricular pressures and time derivatives were measured at baseline and at 30, 60 and 90 s after balloon inflation and 120 s after balloon deflation. RESULTS: Intracoronary electrocardiographic analysis showed that the time course of the maximal ST segment elevation was identical at each inflation, as were wall motion changes assessed by the decrease in septal wall thickening. For the first and last inflations, peak positive dP/dt decreased significantly by 13 +/- 9% (mean +/- SD) and 14 +/- 13%, whereas peak negative dP/dt increased by 23 +/- 15% and 22 +/- 10%, respectively (all p < 0.01 from baseline values). The relaxation time constant, tau, was altered similarly during the different inflations, from 44 +/- 6 to 74 +/- 13 ms and from 57 +/- 13 to 77 +/- 13 ms (all p < 0.001) for the first and last inflations, respectively. Left ventricular end-diastolic pressure increased to the same level after each inflation. In contrast to other hemodynamic variables, tau and left ventricular end-diastolic pressure did not return to baseline values in between the inflations, which may be due to myocardial stunning. CONCLUSIONS: In patients with proximal left anterior descending coronary artery stenosis and no evidence of collateral circulation, brief periods of ischemia, such as those used during routine coronary balloon angioplasty, do not provide any protection against myocardial ischemia.

Aged↗

PubMed1996

Bradykinin pathway is involved in acute hemodynamic effects of enalaprilat in dogs with heart failure.

To determine the role of the renin-angiotensin system and the bradykinin pathway in the mechanism of action of angiotensin-converting enzyme inhibitors in heart failure, the acute effects of enalaprilat (1 mg/kg) were compared with those of a renin inhibitor (ciprokiren, 1 mg/kg i.v.) in 10 chronically instrumented conscious dogs with heart failure induced by right ventricular pacing (3 wk, 240 beats/min). The effects of enalaprilat and ciprokiren on bradykinin infusion (3, 10, and 30 micrograms/min) and the effects of enalaprilat in the presence of the bradykinin B2 receptor antagonist Hoe-140 (10 micrograms/kg i.v.) were also examined. Both inhibitors significantly decreased mean aortic pressure and increased cardiac output. However, enalaprilat induced significantly greater hemodynamic effects than ciprokiren (mean aortic pressure, -13 +/- 3 vs. -6 +/- 1 mmHg; cardiac output, 0.4 +/- 0.1 vs. 0.15 +/- 0.1 l/min). Bradykinin infusion led to dose-dependent decreases in mean aortic pressure and increases in cardiac output that were not modified by pretreatment with ciprokiren but were potentiated 10-fold by enalaprilat. Hoe-140 significantly reduced the hemodynamic effects of enalaprilat. Thus endogenous bradykinin is involved in the acute hemodynamic effects of enalaprilat in experimental heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

Endothelial modulation of beta-adrenergic dilation of large coronary arteries in conscious dogs.

BACKGROUND: Endothelium-derived relaxing factors have been described as important intermediates in beta-adrenergic vasodilation of resistance coronary vessels, but their involvement at the level of large epicardial coronary arteries remains controversial. Therefore, we examined the role of vascular endothelium in the beta-adrenergic-mediated vasodilation of large epicardial coronary arteries in conscious dogs. METHODS AND RESULTS: Nine dogs were instrumented for measurement of left circumflex coronary artery diameter (CD) by sonomicrometry and coronary blood flow velocity (CBFv) with a Doppler technique in response to graded doses of isoproterenol (0.001 to 0.1 microgram/kg IV bolus). Under control conditions, isoproterenol induced dose-dependent increases in CD and CBFv. When CBFv was kept constant at its baseline value by inflation of a cuff occluder, isoproterenol still induced dose-dependent increases in CD, but the latter were of lesser magnitude than those observed under normal CBFv conditions (110 +/- 20 versus 170 +/- 30 microns, respectively, ie, a reduction of 33% of the dilatory response at 0.1 microgram/kg, P < .01). In the same dogs, the coronary endothelium was then mechanically removed at the site of CD measurement by a balloon angioplasty technique. After this procedure, the dose-dependent increases in CD induced by isoproterenol under either normal or controlled CBFv conditions were overimposable, and their magnitude was similar to that of the increases observed in the presence of an intact endothelium when CBFv was kept constant. After beta 1-adrenergic receptor blockade by atenolol (1 mg/kg), isoproterenol-induced increases in CD were abolished either when CBFv was kept constant or after endothelium removal. CONCLUSIONS: In conscious dogs, the direct stimulating effect of isoproterenol on beta 1-adrenergic receptors is endothelium-independent at the level of large coronary arteries. The endothelium reinforces the dilatory response to isoproterenol through an indirect, flow-dependent mechanism.

Adrenergic beta-Agonists↗

PubMed1995

Comparison of the effects of exercise and cold pressor test on the vasomotor response of normal and atherosclerotic coronary arteries and their relation to the flow-mediated mechanism.

This study was designed to assess the vasomotor response of coronary arteries to exercise and the cold pressor test, and its relationships with the endothelium-mediated dependent mechanism. Twenty-two patients were entered in the study. Group I was composed of 12 patients with a total cholesterol level < 200 mg/dl associated with angiographically smooth, normal coronary arteries. Group 2 consisted of 10 patients with both a cholesterol level > 240 mg/dl and angiographic luminal irregularities of the left anterior descending coronary artery. Coronary blood flow was assessed by a 0.018-inch tip guidewire during Doppler ultrasonography, and analysis of the coronary arterial dimension of the midportion of the left anterior descending coronary artery was performed by quantitative coronary angiography. Catecholamine concentrations were assessed at the different stages of the protocol. The rate-pressure product increased during both the cold pressure test and exercise (p < 0.001). Coronary blood flow velocity increased during the cold pressor and exercise tests by 24.5 +/- 10% and 72 +/- 42%, respectively (p < 0.001), and by 127 +/- 62% (p < 0.0001) after administration of papaverine. In group 1, the cold pressor test had a more pronounced vasodilating effect on epicardial coronary arteries (+11.2 +/- 16%) compared with group 2 (-2 +/- 9%, p < 0.05). Similarly, exercise had a vasodilating action in group 1 (11.3 +/- 15%) compared with group 2 (-1.9 +/- 8%, p < 0.05). Both responses were highly correlated (r = 0.92, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Hemodynamic mechanisms responsible for reduced subendocardial coronary reserve in dogs with severe left ventricular hypertrophy.

BACKGROUND: Reduced subendocardial coronary reserve is a hallmark of left ventricular hypertrophy (LVH). The goal of this study was to determine whether hemodynamic, as opposed to structural, mechanisms were responsible for the reduced subendocardial coronary reserve. METHODS AND RESULTS: The effects of near-maximal vasodilation with adenosine were examined in 10 conscious dogs with LVH (79% increase in ratio of LV weight to body weight) induced by aortic banding in puppies with and without preload reduction. At baseline, LV end-diastolic pressure, LV end-diastolic circumferential and compressive radial wall stresses, and LV myocardial blood flow were similar in dogs with LVH and sham-operated controls, while LV end-systolic circumferential wall stress tended to be greater in the LVH group compared with the control group. In control dogs, adenosine reduced LV circumferential end-systolic and end-diastolic wall stresses and compressive radial subendocardial wall stress; LV subendocardial blood flow increased (from 1.41 +/- 0.16 to 3.58 +/- 0.27 mL.min-1.g-1) and the ratio of subendocardial to subepicardial blood flow decrease from 1.30 +/- 0.07 to 0.69 +/- 0.05. In dogs with LVH, during adenosine infusion, LV circumferential end-systolic and end-diastolic wall stresses and LV radial subendocardial wall stresses remained elevated, the increase in LV subendocardial blood flow was significantly smaller (from 1.11 +/- 0.11 to 2.27 +/- 0.24 mL.min-1.g-1, P < .05), and the subendocardial/epicardial ratio fell to a lower level (from 1.22 +/- 0.17 to 0.35 +/- 0.03, P < .05). When LV wall stresses during adenosine were reduced in a subgroup of 5 dogs with LVH, the endocardium/epicardium ratio during adenosine infusion was no longer different from that in control dogs (0.63 +/- 0.11), nor was the level of subendocardial blood flow different (3.42 +/- 0.60 mL.min-1.g-1). CONCLUSIONS: These data suggest that hemodynamic factors, eg, compressive forces, are an important component of the reduced subendocardial coronary reserve as opposed to structural alterations, even in the presence of severe LVH.

Adenosine↗

PubMed1995

Improvement of subendocardial myocardial perfusion after percutaneous transluminal coronary angioplasty. A myocardial contrast echocardiography study with correlation between myocardial contrast reserve and Doppler coronary reserve.

BACKGROUND: After angioplasty coronary reserve improves but does not normalize in most patients. The purpose of this study was to examine before and after angioplasty coronary reserve and transmural myocardial blood flow distribution using myocardial contrast echocardiography. METHODS AND RESULTS: Twelve patients with left anterior descending coronary artery stenosis were investigated before and immediately after angioplasty. A Doppler catheter was placed in the proximal segment. Myocardial contrast echocardiography was performed by imaging the septum in M mode in a parasternal view using a 3.0-mL bolus of sonicated amidotrizoate sodium meglumine through the guiding catheter. The gray level before injection was subtracted from the gray level after injection to maximize contrast time-intensity curves. The area under the curve was used as an indicator of myocardial blood flow, and subendocardial/subepicardial ratios were measured. After baseline measurements were obtained, Doppler and echographic data were recorded after a bolus infusion of papaverine into the left main coronary artery. The same protocol was performed in patients after angioplasty and in five control subjects with normal coronary arteries. Before angioplasty, echocardiographic and Doppler coronary reserve were 2.57 +/- 0.48 and 2.54 +/- 0.57, respectively. Both increased after angioplasty to 3.65 +/- 0.57 and 3.36 +/- 0.70, respectively (P < .05). Coronary reserve values obtained in patients with these two methods under the different conditions and in control subjects were correlated (r = .81; P = .0001). Before angioplasty, subendocardial/subepicardial septal ratios decreased from 0.80 +/- 0.48 to 0.60 +/- 0.27 after papaverine (P < .05). However, after angioplasty, these ratios tended to increase, from 0.72 +/- 0.27 to 0.92 +/- 0.45 after papaverine, but they did not change in control subjects (1.11 +/- 0.23 to 0.92 +/- 0.11). CONCLUSIONS: These results show that myocardial contrast echocardiography yields flow reserve values that correlate with values obtained using intracoronary Doppler. This technique may be considered as an accurate tool to assess coronary reserve in humans.

Angioplasty, Balloon, Coronary↗