Compensatory regional contraction following coronary artery occlusion depends on subendocardial hyperaemia and hyperkinesis.

The effects of circumflex coronary artery occlusion on regional myocardial performance and blood flow in the left ventricular anterior wall was studied, using 16 thoracotomized pentobarbital-anaesthetized cats. Two pairs of ultrasonic crystals were placed in the midwall; one segment (longitudinal) parallel to the subendocardial fibres, the other (circumferential) being aligned to the fibres of the outer half-layer. A shunt line from the right subclavian artery to the main left coronary artery was unrestricted in eight cats (Group A) and clamped in another eight cats (Group B) until coronary perfusion pressure was clearly reduced with only a minor reduction in shunt flow, but without changes in global cardiac function. After circumflex coronary occlusion hyperkinesis was most pronounced in segments parallel to subendocardial fibres (longitudinal), also validated as a marked leftward shift in the end-systolic pressure-length relation of these segments. Such a shift may indicate decreased regional afterloading along the cardiac major axis. Hyperkinesis of longitudinal segments was attenuated in Group B where a fixed shunt stenosis hampered subendocardial and mid-myocardial hyperaemia. The lesser hyperkinesis of Group B was associated with decreased left ventricular systolic pressure and cardiac output. Thus, impaired compensatory contraction outside an acute ischaemic region was produced by a significant coronary stenosis which precluded the subendocardial hyperaemia and hyperkinesis of that region.     

Myocardial contraction patterns in non-ischaemic and ischaemic regions during acute coronary insufficiency

The effect of coronary insufficiency on the myocardial contractionpattern was studied in 11 thoractomized cats using apical longaxis echocardiograms and cross-oriented segments in the anteriormidwall. Myocardial tissue blood flow was studied using radiolabelledmicrospheres. After circumflex coronary artery occlusion, ejectionshortening increased on average 17% for circumferential segments(P<0•05) and 61% for longitudinal segments (P<0•001).Hyperkinesis was also validated as augmented anterior endocardialwall motion and wall thickening. Circumflex occlusion increasedend-systolic sphericity of the left ventricle (P<0•05).Subsequent underperfusion of the left coronary artery, in twodiscrete steps, decreased subendocardial blood flow by, on average,36% (P<0•001) and 75% (P<0•001) vs the post-occlusionvalue, while subepicardial flow did not change. While subendocardialblood flow decreased by 36%, systolic shortening of the globalmajor axis decreased, by, on average, 77% (P<0•001),shortening of the longitudinal segments by 36% (P<0•001),and systolic shortening of the minor axis by 18% (P<0•05),whereas shortening of midwall circumferential segments did notchange. This study shows that changes in myocardial contractionin both non-ischaemic and ischaemic regions during coronaryinsufficiency are most pronounced in the direction of the cardiacmajor axis.     

Analysis of coronary collaterals in ischaemic heart disease by angiography during pacing induced ischaemia.

Studies were made using ordinary selective coronary angiography and angiography during ischaemia produced by right atrial pacing, on a series of 41 patients with ischaemic heart disease, to examine the response of the collaterals to the ischaemia stimulus. Regional myocardial perfusion was determined under the same circumstances by measuring regional 133Xenon washout curves. No collaterals were found in 8 patients, none of whom demonstrated collaterals when angiography was repeated during ischaemia. Eleven of the 33 patients with prepacing collaterals (33%) responded to ischaemia with an increase in the collaterals, 16 patients (49%) showed no change, 5 patients (15%) showed a decrease in the collaterals, and one patient exhibited a bidirectional change. Regional myocardial perfusion responses closely paralleled the angiographic changes, yielding suggestive evidence that the collaterals were intimately involved in the enhancement of the flow. Despite different collateral and flow responses to ischaemia, the data on exercise tolerance, left ventricular end-diastolic pressure, ejection fraction, prevalence of left ventricular asynergy, and the topographic relation between synergy and collaterals, were largely similar. The data show that in some patients the collateral circulation reacts to ischaemia by enhancement, but the functional significance of this response is obscure.     

Ventricular fibrillation during acute coronary occlusion is related to the dilation of the ischemic region

Myocardial stretch induces several electrophysiological changes and arrhythmias, but little is known on its possible role in triggering ventricular fibrillation (VF) during acute coronary occlusion. In thiopental-anesthetized, open-chest pigs submitted to a 40-min ligation of the left anterior descending coronary artery, the association between the early increase in end-diastolic length (measured by means of ultrasonic crystals) in the ischemic region and subsequent VF was analyzed. Animals received no treatment (n = 35) or intravenous nitroglycerin (2.5 μg/kg/min for 20 min, starting 10 min after coronary occlusion, n = 8) or Gd³⁺ (80 μM/kg for 35 min, starting 5 min before occlusion, n = 15). Twenty-four animals (41 %) had VF, 16 to 39 min after coronary occlusion. The magnitude of ischemic dilation and the incidence of VF were similar among groups. End-diastolic length in the ischemic region 15 min after coronary occlusion was 115.7 ± 1.2 % of baseline in animals with VF and 111.4 ± 0.9 % in those without (P = 0.007), and was the strongest predictor of this arrhythmia (P = 0.003) after adjusting for treatment and other possible confounding variables. Thus, the dilation of the ischemic region is closely and independently associated with VF following coronary occlusion. Although the interventions tested in the present study failed to protect against this arrhythmia, the results strongly suggest an influence of ischemic dilation on VF. Received: 11 April 2002, Returned for revision: 21 May 2002, Revision received: 12 June 2002, Accepted: 27 June 2002 Correspondence to: D. Garcia-Dorado, M.D.     

Analysis of coronary collaterals in ischaemic heart disease by angiography during pacing induced ischaemia.

Studies were made using ordinary selective coronary angiography and angiography during ischaemia produced by right atrial pacing, on a series of 41 patients with ischaemic heart disease, to examine the response of the collaterals to the ischaemia stimulus. Regional myocardial perfusion was determined under the same circumstances by measuring regional 133Xenon washout curves. No collaterals were found in 8 patients, none of whom demonstrated collaterals when angiography was repeated during ischaemia. Eleven of the 33 patients with prepacing collaterals (33%) responded to ischaemia with an increase in the collaterals, 16 patients (49%) showed no change, 5 patients (15%) showed a decrease in the collaterals, and one patient exhibited a bidirectional change. Regional myocardial perfusion responses closely paralleled the angiographic changes, yielding suggestive evidence that the collaterals were intimately involved in the enhancement of the flow. Despite different collateral and flow responses to ischaemia, the data on exercise tolerance, left ventricular end-diastolic pressure, ejection fraction, prevalence of left ventricular asynergy, and the topographic relation between synergy and collaterals, were largely similar. The data show that in some patients the collateral circulation reacts to ischaemia by enhancement, but the functional significance of this response is obscure.     

Compensatory enlargement of human coronary arteries during progression of atherosclerosis is unrelated to atheroma burden: serial intravascular ultrasound observations from the REVERSAL trial.

AIMS: On the basis of the evidence from autopsy studies, it is accepted that compensatory enlargement (remodelling) of coronary arteries during progression of atherosclerosis diminishes once atheroma burden (cross-sectional area stenosis) reaches approximately 40%. Our aim was to evaluate whether atheroma burden is a limiting factor for coronary arterial remodelling using in vivo serial intravascular ultrasound (IVUS). METHODS AND RESULTS: From the cohort of the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, we identified 210 focal coronary lesions at baseline IVUS. Of these, 128 lesions that had an increase in atheroma area at the 18-month follow-up IVUS were included in the analysis. Lesions were matched at baseline and follow-up. The increase in external elastic membrane (EEM) area for each mm(2) increase in atheroma area was not significantly different in lesions with <40 and >or=40% atheroma burden at baseline (1.62 vs. 1.28 mm(2), P=0.30). There were no correlations between atheroma burden at baseline and change in EEM (r=0.02, P=0.86) or change in lumen (r=0.04, P=0.64) areas. CONCLUSION: Assessment of coronary arterial remodelling by serial IVUS revealed that compensatory remodelling is not limited by atheroma burden. Atheroma burden is not a determinant of arterial enlargement during the progression of atherosclerosis.     

Helicobacter pylori is an aetiological factor for ischaemic heart disease: the case in favour.

The evidence to date concerning the association between Helicobacter pylori infection and coronary heart disease is consistent with a modest increased risk. Research is currently being undertaken into factors which may modify this association. Probably, there is sufficient evidence given the ease of the proposed intervention to make it worthwhile to undertake a trial of eradication therapy.     

Occlusion time dependency of regional noradrenaline release and cardiac arrhythmias during reperfusion of acutely ischaemic heart in the dog in vivo

STUDY OBJECTIVE--The aim was to study the occlusion time dependency of reperfusion induced increases in regional cardiac noradrenaline release from the ischaemic area in relation to the incidence of ventricular arrhythmias. DESIGN--The left anterior descending coronary artery was ligated for 15, 30 and 60 min in three separate groups of dogs (n = 10 per group). Each occlusion period was followed by a 30 min reperfusion period. The coronary sinus and the epicardial vein running in parallel with the left anterior descending coronary artery were cannulated for measurement of noradrenaline and lactate. EXPERIMENTAL MATERIAL--30 adult mongrel dogs, 22.5(SEM 1.1) kg, were used for the study. The animals were anaesthetised with sodium pentobarbitone. MEASUREMENTS AND MAIN RESULTS--During occlusion, epicardial venous blood noradrenaline concentrations remained unchanged up to 30 min, but increased from 0.133(0.027) ng.ml-1 to 0.289(0.069) ng.ml-1 after 60 min of occlusion (p less than 0.05). However, epicardial venous blood lactate concentrations increased immediately upon occlusion, and remained elevated (p less than 0.05) during the whole period of occlusion in all groups. Neither noradrenaline nor lactate concentrations in coronary sinus blood increased during occlusion. During reperfusion, nine dogs showed early ventricular fibrillation. The highest incidence of fibrillation (n = 5/10) was found in the 15 min occlusion group, but the difference was not significant between groups. Epicardial venous blood noradrenaline concentrations increased to 0.371(0.076) ng.ml-1, 0.470(0.178) ng.ml-1, and 1.824(0.713) ng.ml-1 upon reperfusion following 15, 30 and 60 min occlusion, respectively (each p less than 0.05). Maximum increases in epicardial venous blood noradrenaline concentrations during reperfusion were correlated with duration of preceding occlusion (r = 0.60, n = 21, p less than 0.01). Maximum increases in mean arrhythmic ratios observed during the first 10 min of reperfusion were proportionally related to mean epicardial venous blood noradrenaline concentrations. The increases in epicardial venous blood noradrenaline concentrations and the incidence of ventricular arrhythmias in the 60 min occlusion group were greater (p less than 0.05) than in the other two groups. CONCLUSIONS--This study shows that noradrenaline is released progressively from the ischaemic area during occlusion for 60 min. The amount of noradrenaline washed out upon reperfusion and the incidence of reperfusion ventricular arrhythmias both appear to be dependent upon duration of preceding occlusion. The results suggest that cardiac noradrenaline released locally from the ischaemic region may contribute to the genesis of reperfusion ventricular arrhythmias, but not to that of reperfusion ventricular fibrillation.     

Effects of molsidomine during the cold test in stable coronary insufficiency under beta-blocker treatment

The heart rate, cardiac output, coronary sinus blood flow, systolic and end diastolic left ventricular pressures, femoral arterial pressure and coronary oxygen arterio-venous difference were measured in 12 patients with stable coronary artery disease without cardiac failure on long-term betablocker therapy, before and 45 minutes after 2 or 3 mg sublingual molsidomine. The measurements were repeated in 8 patients during a cold pressor test. Under basal conditions, molsidomine decreased the systolic and end diastolic left ventricular pressures, mean femoral arterial pressure, cardiac output and double product. The coronary oxygen arterio-venous difference was unchanged. Coronary sinus flow and myocardial oxygen consumption decreased. In the 2 patients who were given 3 mg molsidomine, a progressive reduction in systolic left ventricular pressure to 70% or less than its initial value, necessitated immediate treatment with volume expanders. During the cold pressor test before molsidomine the systolic and end diastolic left ventricular pressures, mean femoral arterial pressure and the double product increased. Coronary sinus flow was unchanged overall: it decreased in 6 patients, increased in 2 patients and remained the same in 1 patient. Coronary resistance increased in 6 patients and decreased in only one patient. During the cold pressor test after molsidomine there was a significant reduction in the increase of systolic left ventricular pressure, mean femoral artery pressure and double product. Coronary sinus blood flow increased in 5 patients and decreased in only one case. Coronary resistance decreased in half the cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Value of the negative U wave during exercise test in the diagnosis of coronary insufficiency

In order to determine the value of inversion of the U wave during exercise for the diagnosis of coronary insufficiency, the stress tests of 227 patients were reviewed and confronted with the results of coronary angiography which showed 93 subjects with angiographically normal arteries and 134 subjects with left anterior descending disease; 37 patients had single vessel disease (Group I), 38 had double vessel disease (Group II) and 59 had triple vessel disease (Group III). When compared to the two classical criteria, anginal pain and less than or equal to 1 mm ST depression, inversion of the U wave was more specific: 82.8 +/- 7.6 p. 100 vs 77.4 p. 100 for anginal pain, and 66.7 +/- 9.6 p. 100 for ST depression. The sensitivity of this new sign for the detection of coronary insufficiency was 26.9 +/- 7.5 p. 100 vs 80.6 +/- 6.7 p. 100 for ST depression and 56.7 +/- 8.4 p. 100 for anginal pain. The positive predictive value of U wave inversion on effort was 70.9 +/- 12 p. 100 compared to 77.7 +/- 6.9 p. 100 for ischaemic ST depression and 78.3 +/- 8.2 p. 100 for induced anginal pain. Conversely, in angiographically normal coronary arteries, the absence of U wave inversion had a negative predictive value of 44.8 +/- 7.4 p. 100 compared to 70.5 +/- 9.5 p. 100 for the absence of ischaemic ST changes and 55.4 +/- 8.5 for the absence of anginal pain. These results confirm previously published data.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic and coronary effects of molsidomine in patients with stable coronary insufficiency in the basal state, during an atrial stimulation test and a cold test

The heart rate (HR), the cardiac output (Qc) and the coronary sinus flow rate (Qcs), the left ventricular systolic and end-diastolic pressures (LVSP, LVEDP), the femoral artery pressure (FAP) and the difference between the coronary arterial and coronary venous oxygen tension (DAVcO2) were measured in patients with stable coronary insufficiency without cardiac failure, before and 40 to 60 minutes after 2 or 3 mg of molsidomine (M). In 20 patients, these measurements were made in the basal state, in spontaneous rhythm (SP). In 8 of these patient, (including 3 receiving beta-blockers) the measurements were made during an atrial stimulation test (ST) and in 8 other patients, all receiving long-term beta-blocker therapy, the measurements were made during a cold test (CT). At the basal state in SR, a gradual reduction in the LVSP to 70% or less of its initial value was observed in the patients receiving 3 mg of M (2 of whom received beta-blocker treatment). The LVSP was immediately restored by vascular filling. In 16 patients, M decreased the LVSP, the LVEDP, the FAP, the Qc and the double product (DP = LVSP X HR). The DAVcO2 was unchanged. Qcs and MVO2 (MVO2 = Qcs X DAVcO2) were decreased. In the course of ST, the haemodynamic and coronary changes are similar to those seen in the basal state. During the Ct, the increase in the LVSP, FAP and DP was significantly reduced by M. The variations in Qcs and coronary resistance (FAP/Qcs) were also significantly different after M., with better metabolic regulation of the coronary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)