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Biomedical subjects

G Heusch

Publications and source records attributed to G Heusch.

At least 73 records · Page 4Linked to original sources
PubMed1999

G protein beta3 subunit 825T allele and enhanced coronary vasoconstriction on alpha(2)-adrenoceptor activation.

Recently, alpha(2)-adrenoceptor activation was shown to play an important role in the vasoconstriction of normal coronary arteries, whereas in the presence of atherosclerosis, the activation of both alpha(1)- and alpha(2)-adrenoceptors reduces coronary blood flow in humans. alpha(2)-Adrenoceptors activate pertussis toxin (PTX)-sensitive G proteins, whereas alpha(1)-adrenoceptors couple to PTX-insensitive G proteins. Thus, the 825T allele of the beta3 subunit of heterotrimeric G proteins, associated with enhanced PTX-sensitive G protein signaling, was expected to determine the alpha(2)-adrenoceptor-, but not the alpha(1)-adrenoceptor-, mediated reduction in coronary blood flow (CBF). Genotyping was performed on 48 individuals. Twelve of the 48 received the alpha(1)-adrenoceptor agonist methoxamine (MTX; 5 mg IC), and 12 received the alpha(2)-adrenoceptor agonist BHT 933 (BHT; 5 mg IC). Twenty-four additional individuals received both MTX and BHT during the same investigational procedure. CBF was calculated on the basis of coronary angiography and intracoronary Doppler flow velocity measurement. Drug-related ischemia was assessed on the basis of ST-segment changes and angina pectoris. In response to BHT, but not to MTX, CBF was reduced to a significantly greater extent in 825T allele carriers (58+/-4%, n=16) than in individuals homozygous for the C825 allele (28+/-4%, n=19, P=0.001). This finding was independent of cholesterol levels, mean arterial blood pressure, and the presence or absence of coronary artery disease. Ischemic events in response to BHT occurred more frequently in 825T allele carriers than in homozygous 825C allele carriers (P=0.01). alpha(2)-Adrenoceptor coronary vasoconstriction is genetically determined and significantly enhanced in GNB3 825T allele carriers.

Adrenergic alpha-Agonists↗
PubMed1999

Augmented alpha-adrenergic constriction of atherosclerotic human coronary arteries.

BACKGROUND: Although adrenergic activation plays a major role in the initiation of experimental myocardial ischemia, the significance of alpha-adrenergic coronary constriction in humans has been questioned. The present study assessed the impact of selective alpha-adrenergic receptor activation in patients with normal or atherosclerotic coronary arteries. METHODS AND RESULTS: In 39 patients, coronary blood flow (CBF, mL/min) was determined from combined angiography and Doppler measurements. In 8 patients with normal coronary arteries (group 1) and 9 with single coronary artery stenosis (group 2), doses of 1, 2.5, 5, and 10 mg IC of the alpha1-agonist methoxamine (M) were injected. Identical doses of the alpha2-agonist BHT933 (B) were injected in 8 patients with normal coronary arteries (group 3) and 8 with single stenosis (group 4). In 6 additional patients with single stenosis (group 5), aortocoronary sinus lactate differences were measured in response to M and B. CBF remained unchanged in group 1. In contrast, CBF was decreased dose-dependently in group 2, with a maximum at 10 mg M (39.0+/-9.4 versus 15.2+/-7.0). In groups 3 and 4, CBF was also decreased dose-dependently, with a maximum at 10 mg B (63.3+/-24.8 versus 49. 1+/-27.9 and 41.5+/-19.0 versus 12.7+/-8.0, respectively). In group 5, there was more net lactate production with B than with M (-0. 34+/-0.11 versus -0.04+/-0.09 mmol/L). CONCLUSIONS: In normal coronary arteries, alpha1-adrenergic activation does not reduce CBF, whereas alpha2-adrenergic activation reduces CBF by microvascular constriction. Both alpha1- and alpha2-adrenergic epicardial and microvascular constriction are augmented by atherosclerosis and can induce myocardial ischemia.

Adrenergic alpha-Agonists↗
PubMed1999

Alpha-adrenergic blockade improves recovery of myocardial perfusion and function after coronary stenting in patients with acute myocardial infarction.

BACKGROUND: AMI reperfusion by thrombolysis does not improve TIMI flow and LV function. The role of infarct-related artery (IRA) stenosis and superimposed changes in coronary vasomotor tone in maintaining LV dysfunction must be elucidated. METHODS AND RESULTS: Forty patients underwent diagnostic angiography 24 hours after thrombolysis. Seventy-two hours after thrombolysis, the culprit lesion was dilated with coronary stenting. During angioplasty, LV function was monitored by transesophageal echocardiography. Percent regional systolic thickening was quantitatively assessed before PTCA, soon after stenting, 15 minutes after stenting, and after phentolamine 12 microg/kg IC (n=10), the alpha1-blocker urapidil 600 microg/kg IV (n=10), or saline (n=10). Ten patients pretreated with beta-blockers received urapidil 10 mg IC. Coronary stenting significantly improved thickening in IRA-dependent and in non-IRA-dependent myocardium (from 27+/-15% to 38+/-16% and from 40+/-15% to 45+/-15%, respectively). Simultaneously, TIMI frame count decreased from 39+/-11 and 40+/-11 in the IRA and non-IRA, respectively, to 23+/-10 and 25+/-7 (P<0.05). Fifteen minutes after stenting, thickening worsened in both IRA- and non-IRA-dependent myocardium (to 19+/-14% and 28+/-14%, P<0.05), and TIMI frame count returned, in both the IRA and non-IRA, to the values obtained before stenting. Phentolamine and urapidil increased thickening to 36+/-17% and 41+/-14% in IRA and to 48+/-11% and 49+/-17% in non-IRA myocardium respectively, and TIMI frame count decreased to 16+/-6 and to 17+/-5, respectively. Changes were attenuated with beta-blocker pretreatment. CONCLUSIONS: Our finding that alpha-adrenergic blockade attenuates vasoconstriction and postischemic LV dysfunction supports the hypothesis of an important role of neural mechanisms in this phenomenon.

Adrenergic alpha-Antagonists↗
PubMed1999

Unique cardioprotective action of the new calcium antagonist mibefradil.

BACKGROUND: Mibefradil is a calcium antagonist with few negative inotropic effects at therapeutic concentrations. METHODS AND RESULTS: The effect of mibefradil on infarct size (IS) was compared with those of placebo, amlodipine, and verapamil in 64 anesthetized pigs. In placebo pigs, after 90 minutes of ischemia and 120 minutes of reperfusion, IS (by triphenyl tetrazolium chloride staining) was 15.3+/-10.8% (SD) of the area at risk. Mibefradil (0.60 mg/kg IV) reduced heart rate and left ventricular (LV) pressure, and IS was 1. 9+/-3.9% (P<0.05 versus placebo). Verapamil (0.15 mg/kg IV) also decreased heart rate, LV pressure, and IS (6.1+/-4.2%, P<0.05 versus placebo). Amlodipine (0.20 mg/kg IV) did not alter heart rate, LV pressure, or IS (9.9+/-5.4%, P=NS versus placebo). When heart rate was maintained constant by left atrial pacing and LV pressure was adjusted to that of the placebo group by an intra-aortic balloon, mibefradil still decreased IS (3.8+/-3.0%, P<0.05 versus placebo), but verapamil did not (11.6+/-8.3%, P=NS versus placebo). With glibenclamide infusion, mibefradil no longer reduced IS (13.1+/-4.3% versus 17.8+/-5.6% with glibenclamide alone, P=NS). CONCLUSIONS: The IS-limiting effect of mibefradil, in contrast to that of verapamil, was not dependent on favorable hemodynamics but was abolished by glibenclamide, suggesting a direct cardioprotective action of mibefradil.

Amlodipine↗
PubMed1999

Diastolic dysfunction and collagen structure in canine pacing-induced heart failure.

Heart failure is characterized not only by systolic, but also by diastolic dysfunction. The present study tested whether or not diastolic dysfunction is associated with changes in tissue properties and collagen network structure. Heart failure was induced in seven chronically instrumented, conscious dogs by rapid left ventricular pacing (2 50 min(-1)). After 2-5 [mean: 4+/-1 (S.D.)] weeks pacing, heart failure was apparent from clinical symptoms (ascites, cachexia, edema, exercise intolerance) and hemodynamic parameters (significant increases of heart rate and left ventricular end-diastolic pressure and decreases of left ventricular maximal pressure, dP/dtmax and systolic wall thickening). The left ventricle was dilated, as indicated by a decrease of end-diastolic wall thickness (6.3+/-2.0 v 7.2+/-2.1 mm; P<0.05; sonomicrometry). The left ventricular end-diastolic pressure-strain relation (strain: relative change of end-diastolic wall thickness) was obtained during alterations of loading conditions by inferior caval vein and descending thoracic aortic occlusion. The slope of this relation increased from 85+/-20 to 428+/-188 in heart failure, indicating an increase of left ventricular stiffness. Collagen was stained with picrosirius red and analyzed using polarized light microscopy. In heart failure, the collagen volume fraction remained unchanged (1.9+/-1.2 v 2.3+/-1.3%; N.S.), while the nonuniformity of collagen orientation, as reflected by its standard deviation, was increased (11.1+/-1.8 v 6.1+/-0.4 o; P<0.05). The nonuniformity of collagen fiber orientation correlated with left ventricular stiffness [r=0.75].

Animals↗
PubMed1999

Quantification of cardioprotective gene expression in porcine short-term hibernating myocardium.

Several cardioprotective proteins are induced during myocardial ischemia, such as heat shock proteins and anti-apoptotic Bcl-2-related proteins which, when experimentally overexpressed, have been shown to prevent ischemia-induced myocyte loss. As this pathophysiological induction is obviously not sufficient to prevent losses of myocytes, we analysed whether it could occur under moderate myocardial ischemia with hibernation, thus potentially contributing to myocyte protection under these conditions. Therefore, using anesthetized pigs with documented myocardial hypoperfusion and short-term hibernation, we investigated the left ventricular mRNA expression of the inducible heat shock protein Hsp70 and of the anti-apoptotic Bcl-XL in comparison with the pro-apoptotic Bak and Fas expression. For transcriptional analyses, the porcine cDNA sequences of Bcl-XL, Bak and Fas were identified by polymerase chain reaction (PCR) or by screening of a porcine heart cDNA library and cloned. Using reverse transcription polymerase chain reaction (RT-PCR), we observed an unchanged mRNA expression of inducible Hsp70, Bcl-XL, Bak and Fas after 85 min of hypoperfusion in the short-term hibernating myocardium, as well as after 30 min of subsequent reperfusion in the stunned myocardium, compared with transcription in a non-hypoperfused control area of the same ventricle. In conclusion, the mRNA expression of inducible Hsp70 and of several apoptosis-modulating proteins is not altered during moderate myocardial ischemia resulting in short-term hibernation of the affected area and during subsequent stunning.

Amino Acid Sequence↗
PubMed1999

The relation of contractile function to myocardial perfusion. Perfusion-contraction match and mismatch.

During normoperfusion, both myocardial blood flow and contractile function are heterogeneously distributed throughout the left ventricle. Midwall segment shortening is greater at the apex than at the base of the left ventricle, and greater in the anterior than in the posterior wall. Also, transmural heterogeneity of myocardial deformation exists, with greater segment shortening and wall thickening in inner than in outer myocardial layers. Myocardial blood flow is greater in inner than in outer myocardial layers. Apart from transmural heterogeneities, there are adjacent regions with largely different resting flow in the same heart. While an increase in myocardial contractile function will lead to a metabolically mediated increase in myocardial blood, an increase in regional coronary perfusion within or above the autoregulatory range does not increase regional myocardial contractile function. During hypoperfusion induced by a proximal coronary stenosis, the reduction in subendocardial blood flow is more pronounced than that in subepicardial blood flow, and contractile function in the inner myocardial layers ceases more rapidly than in the outer myocardial layers. The reduced regional myocardial contractile function is closely matched to the reduced regional myocardial blood flow; however, such a coupling between reduced flow and function is lost when ischemia is prolonged for several hours in that function for a given flow is further reduced. Also, acute embolization of the coronary microcirculation induces a progressive loss of regional myocardial function at an unchanged regional myocardial blood flow, i.e. perfusion-contraction mismatch. During reperfusion, regional myocardial contractile function remains depressed for a prolonged period of time, depending on the severity, duration and location of the preceding ischemic episode, while regional myocardial blood flow is restored to almost normal. Recovery of contractile function in the outer myocardial layers is faster than in the inner myocardial layers.

Animals↗
PubMed1999

Coronary microembolization--its role in acute coronary syndromes and interventions.

The diagnosis coronary artery disease is classically based on patient's symptoms and morphology, as analyzed by angiography. The importance of risk factors for the development of coronary atherosclerosis and disturbance of coronary vasomotion is clearly established. However, microembolization of the coronary circulation has also to be taken into account. Microembolization may occur as a single or as multiple, repetitive events, and it may induce inflammatory responses. Spontaneous microembolization may occur, when the fibrous cap of an atheroma or fibroatheroma (Stary i.v. and Va) ruptures and the lipid pool with or without additional thrombus formation is washed out of the atheroma into the microcirculation. Such events with progressive thrombus formation are known as cyclic flow variations. Plaque rupture occurs more frequently than previously assumed, i.e. in 9% of patients without known heart disease suffering a traffic accident and in 22% of patients with hypertension and diabetes. Also, in patients dying from sudden death microembolization is frequently found. Patients with stable and unstable angina show not only signs of coronary plaque rupture and thrombus formation, but also microemboli and microinfarcts, the only difference between those with stable and unstable angina being the number of events. Appreciation of microembolization may help to better understand the pathogenesis of ischemic cardiomyopathy, diabetic cardiomyopathy and acute coronary syndromes, in particular in patients with normal coronary angiograms, but plaque rupture detected by intravascular ultrasound. Also, the benefit from glycoprotein IIb/IIIa receptor antagonist is better understood, when not only the prevention of thrombus formation in the epicardial atherosclerotic plaque, but also that of microemboli is taken into account. Microembolization also occurs during PTCA, inducing elevations of troponin T and I and elevations of the ST segment in the EKG. Elevated baseline coronary blood flow velocity, as a potential consequence of reactive hyperemia in myocardium surrounding areas of microembolization, is more frequent in patients with high frequency rotablation than in patients with stenting and in patients with PTCA. The hypothesis of iafrogenic microembolization during coronary interventions is now supported by the use of aspiration and filtration devices, where particles with a size of up to 700 microns have been retrieved. In the experiment, microembolization is characterized by perfusion-contraction mismatch, as the proportionate reduction of flow and function seen with an epicardial stenosis is lost and replaced by contractile dysfunction in the absence of reduced flow. The analysis of the coronary microcirculation, in addition to that of the morphology and function of epicardial coronary arteries, and in particular appreciation of the concept of microembolization will further improve the understanding of the pathophysiology and clinical symptoms of coronary artery disease.

Angioplasty, Balloon, Coronary↗
PubMed1999

Attenuation of myocardial stunning by the AT1 receptor antagonist candesartan.

The effect of AT1 receptor blockade on myocardial stunning is still somewhat ambiguous. In some prior studies, coronary occlusion was of too long duration such that the effects of infarction and stunning on the recovery of contractile function could not be distinguished. In others, blood pressure was decreased such that the improved wall excursion could be the consequence of reduced afterload and/or of attenuated stunning. The present study, therefore, investigated the effect of the AT1 receptor antagonist candesartan in a pure model of myocardial stunning with controlled systemic hemodynamics. Fourteen anesthetized open-chest dogs were subjected to 15 minutes occlusion of the left circumflex coronary artery (LCx) and 4 hours subsequent reperfusion. Systemic hemodynamics (micromanometer), regional myocardial blood flow (colored microspheres), and posterior wall thickening (PWT, sonomicrometry) were measured, and data were compared between 7 placebo controls (group 1) and 7 dogs receiving 1 mg/kg candesartan i.v. before LCx occlusion (group 2). Left ventricular peak pressure was kept constant by an intra-aortic balloon, and heart rate did not change throughout the protocol. Regional myocardial blood flow was not different between the groups under control conditions, increased in response to candesartan in group 2 (posterior subendocardial blood flow from 0.99 +/- 0.18 to 1.57 +/- 0.45; p < 0.05 vs. control conditions), but was not different during myocardial ischemia and at 4 hours of reperfusion between the groups. Under control conditions and during myocardial ischemia, PWT was also not different between the groups. At 4 hours of reperfusion, PWT was still depressed in group 1 (-1.5 +/- 3.4% vs. 17.7 +/- 5.6% during control conditions, p < 0.05), whereas PWT had recovered in group 2 (11.4 +/- 3.7% at 4 hours reperfusion vs. 18.3 +/- 2.7 during control conditions, NS, p < 0.05 vs. group 1). In conclusion, pretreatment with the AT1 receptor antagonist candesartan improved the functional recovery of reperfused myocardium. This attenuation of myocardial stunning was not based on more favorable systemic hemodynamics or regional myocardial blood flow.

Angiotensin Receptor Antagonists↗
PubMed1999

Endotoxin and ischemic preconditioning: TNF-alpha concentration and myocardial infarct development in rabbits.

Ischemic preconditioning (IP) and prior exposure to lipopolysaccharides (LPS) reduce infarct size (IS) and serum tumor necrosis factor-alpha (TNF-alpha) concentration resulting from myocardial ischemia-reperfusion in rabbits. The decrease in TNF-alpha might relate to an induced TNF-alpha inhibitory serum activity (TNF-alpha-ISA). We analyzed TNF-alpha and TNF-alpha-ISA during 30 and 180 min ischemia and reperfusion, respectively, in anesthetized rabbits either untreated (group 1, n = 7), preconditioned (5 and 10 min ischemia and reperfusion, respectively, group 2, n = 9), or exposed to LPS 72 h before ischemia (group 3, n = 9). TNF-alpha-ISA was assessed by coincubating LPS-stimulated rabbit blood with serum of groups 1-3 and measuring TNF-alpha (WEHI assay). With a comparable area at risk, IS in group 1 was 36.9 +/- 11.1 (SD)%, and it was reduced to 13.1 +/- 11.6% and 17.3 +/- 11.3% (both P < 0.05) in groups 2 and 3, respectively. TNF-alpha was increased during ischemia-reperfusion in group 1 but remained unchanged in rabbits subjected to IP or LPS. TNF-alpha-ISA was detected during ischemia-reperfusion in group 2 (29% and 38% of maximum inhibition, respectively) and during baseline, ischemia and reperfusion in group 3 (51%, 46%, 48% of maximum inhibition, respectively) but was absent in group 1. Cardioprotection by IP and LPS is associated with a reduced TNF-alpha and an induced TNF-alpha-ISA during ischemia-reperfusion.

Animals↗
PubMed1999

AT1 receptor blockade in experimental myocardial ischemia/reperfusion.

The renin-angiotensin system is activated during myocardial ischemia, and local angiotensin II formation occurs in ischemic hearts. At least two angiotensin II receptor subtypes, the AT1 and the AT2 receptor, have been identified. The cardiovascular effects of angiotensin II have been attributed largely to activation of AT1 receptors. In ventricular preparations from normal rat and pig hearts, the density of AT1 receptors is higher than that of AT2 receptors, whereas data on the AT receptor subtype density and its distribution in human hearts remain controversial. AT1 receptor blockade increases coronary blood flow during ischemia in dogs and during reperfusion in rats, reduces the incidence of ischemia-related arrhythmias in rats and guinea pigs, limits infarct size in pigs, improves functional and metabolic recovery after myocardial ischemia, and attenuates ventricular remodeling post-myocardial infarction in rats. The potential mechanisms responsible for the cardioprotection by AT1 receptor blockade remain to be elucidated in detail, but appear to involve AT2 receptor activation and the subsequent action of bradykinin, prostaglandins, and/or nitric oxide. Patients under treatment with AT1 receptor blockers for indications such as hypertension and ventricular dilation after myocardial infarction are likely to have improved prognosis when suffering an acute myocardial infarction.

Angiotensin Receptor Antagonists↗
PubMed1998

Infarct size reduction by AT1-receptor blockade through a signal cascade of AT2-receptor activation, bradykinin and prostaglandins in pigs.

OBJECTIVE: We studied the effect of the angiotensin II type 1 (AT1)-receptor antagonist candesartan on infarct size resulting from regional myocardial ischemia in pigs. BACKGROUND: The effects of AT1-receptor blockade on infarct size in different species remain controversial and its potential cardioprotective mechanisms are still unclear. In pigs, infarct development closely resembles that observed in humans. METHODS: A total of 62 enflurane-anesthetized pigs underwent a protocol of 90-min low-flow ischemia and 120-min reperfusion. Systemic hemodynamics (micromanometer), regional myocardial function (sonomicrometry), regional myocardial blood flow (microspheres) and infarct size (TTC [triphenyl tetrazolium chloride]-staining) were determined. RESULTS: Left ventricular peak pressure decreased with candesartan (1 mg/kg i.v.) from 97+/-2 standard error of the mean (SEM) to 86+/-5 mm Hg and was then readjusted by aortic banding. In placebo pigs (n=9), infarct size was 21.8+/-4.8% of the area at risk. Candesartan (n=7) reduced infarct size to 9.7+/-2.5% (p < 0.05). Pretreatment with the AT2-receptor antagonist PD123319 (3 microg/kg/min intracoronarily [i.c.]; n=8), the bradykinin B2-receptor antagonist HOE140 (0.01 microg/kg/min i.c.; n=8) or the cyclooxygenase inhibitor indomethacin (10 mg/kg i.v.; n= 8) per se did not affect infarct size but did abolish the reduction of infarct size achieved by candesartan (PD123319 + candesartan (n=7): 23.2+/-4.7%; HOE140 + candesartan (n=7): 18.2+/-4.0%; indomethacin + candesartan (n=8): 21.1+/-5.2%). Hemodynamics, regional myocardial blood flow during ischemia and the area at risk were comparable among all groups of pigs. CONCLUSIONS: Reduction of infarct size by the AT1-receptor antagonist candesartan in pigs involves angiotensin II type 2 receptor (AT2) activation, bradykinin and prostaglandins.

Angiotensin Receptor Antagonists↗
PubMed1998

Ischemic preconditioning in pigs: a graded phenomenon: its relation to adenosine and bradykinin.

BACKGROUND: A threshold concept for ischemic preconditioning (IPc) has been proposed. It is unclear, however, whether IPc, above a certain threshold, is an all-or-nothing or a graded phenomenon. METHODS AND RESULTS: In 71 enflurane-anesthetized swine, severe left anterior descending coronary artery hypoperfusion for 90 minutes followed by 2 hours of reperfusion resulted in an infarct size (IS, by triphenyltetrazolium chloride) of 16.7+/-3.4% (SEM) of the area at risk. IPc by 2 minutes of low-flow ischemia and 15 minutes of reperfusion before the 90-minute target ischemia did not reduce IS (21.9+/-7.0%). IS was decreased to 9.0+/-2.6% (P<0.05) by 3 minutes of IPc and reduced further to 1.9+/-0.9% (P<0.05) by 10 minutes of IPc. The interstitial adenosine concentration (microdialysis, high-performance liquid chromatography) was unchanged with 2 and 3 minutes of IPc but increased with 10 minutes of IPc (by 573+/-144%). The interstitial bradykinin concentration (microdialysis, radioimmunoassay) remained unchanged with 2 minutes of IPc but increased to a similar extent with 3 minutes (by 198+/-32%) and 10 minutes (by 224+/-30%) of IPc. The IS reduction by 3 minutes of IPc was abolished by blockade of the bradykinin B2 receptor with intracoronary HOE 140 (16.6+/-4.3%) but not with intracoronary infusion of adenosine deaminase (8.4+/-2.5%, P<0.05). HOE 140, however, did not affect the IS reduction (3.5+/- 1.1%, P<0.05) by 10 minutes of IPc. Combined infusion of HOE 140 and adenosine deaminase abolished the IS reduction by 10 minutes of IPc (15.4+/-6.7%). CONCLUSIONS: IS reduction by IPc is a graded phenomenon. Whereas bradykinin is essential during preconditioning ischemia of shorter duration, adenosine is more important during preconditioning ischemia of longer duration.

Adenosine↗
PubMed1998

Improved assessment of coronary stenosis severity using the relative flow velocity reserve.

BACKGROUND: Myocardial fractional flow reserve (FFR) is based on pressure measurements. We have now sought to establish a Doppler-based concept of relative flow velocity reserve (RFVR) for the functional assessment of stenosis severity in epicardial coronary arteries. A clear threshold value to discriminate the functional severity of a coronary stenosis does not exist for coronary flow velocity reserve (CVR) based on intracoronary Doppler measurements. In contrast, the concept of FFR, which is based on intracoronary pressure measurements, has been extensively validated. An FFR value below 0.75 reliably indicates a significant stenosis. METHODS AND RESULTS: RFVR is calculated as the ratio between distal CVR in the stenosed target vessel and distal CVR in a nonstenotic reference vessel. In 21 patients, RFVR was determined in 24 target vessels by use of intracoronary adenosine and correlated to the FFR, determined as the ratio of mean poststenotic to aortic pressures, in the target vessel. Stenosis severity was classified according to quantitative coronary angiography analysis. Reference diameter was 3.0+/-0.4 mm (mean+/-SD), and area stenosis was 74+/-15% (range, 40% to 95%). CVRs in the target and reference vessels were 2.1+/-0.5 and 2.6+/-0.7, respectively. FFR ranged from 0.49 to 0.99 (mean, 0.81+/-0.15) and RFVR from 0.53 to 1.0 (mean, 0.82+/-0.13). Poststenotic CVR did not correlate with either percent area stenosis (r=0.27, P=NS) or FFR (r=0.33, P=NS). In contrast, FFR as well as RFVR showed a curvilinear relation to percent area stenosis (r=0.89, P<0.0001 and r=0.79, P<0.0001, respectively). There was a close linear correlation between FFR and RFVR (r=0.91, P<0.0001). CONCLUSIONS: RFVR correlates closely to FFR and to percent area stenosis, whereas the correlation of CVR with FFR and percent area stenosis is rather poor. RFVR is a promising new concept for assessment of coronary stenosis severity and clinical decision making based on Doppler measurements.

Aged↗
PubMed1998

Positron emission tomography analysis of [1-(11)C] acetate kinetics in short-term hibernating myocardium.

BACKGROUND: Modeling of the time-[1-(11)C]acetate activity curve assumes a constant concentration of labeled tricarboxylic acid cycle intermediates and associated metabolites, such as glutamate and aspartate, which may, however, decrease in short-term hibernating myocardium. METHODS AND RESULTS: In 12 anesthetized pigs, [1-(11)C]acetate was injected as a bolus into the cannulated left anterior descending coronary artery during normoperfusion, inotropic stimulation, and early (5 to 45 minutes) and prolonged ischemia (60 to 90 minutes). Regional myocardial oxygen consumption (MVO2, microliters per minute per gram) was measured, and the absence of necrosis was verified by triphenyl tetrazolium chloride staining. Inotropic stimulation increased MVO2 from 52.5+/-7.4 to 195.4+/-36.2 (mean+/-SD) and the rate constant (kmono, minutes[-1]) of [1-(11)C]acetate clearance from 0.094+/-0.018 to 0.322+/-0.076. During early ischemia, MVO2 and kmono were decreased to 24.3+/-8.5 and 0.061+/-0.011, respectively. Kmono closely correlated to MVO2 during normoperfusion, inotropic stimulation, and early ischemia. In short-term hibernating myocardium, however, at an unchanged MVO2, kmono increased toward control values (0.080+/-0.014). Myocardial glutamate and aspartate concentrations (biopsies) decreased to 47+/-26% and 77+/-18%; the peak count rate decreased to 66+/-22% of its respective control value. After correction for the decreases in glutamate and aspartate or in peak count rate, kmono was again decreased (0.050+/-0.016 or 0.052+/-0.014, respectively), and a close relationship to MVO2 was restored. CONCLUSIONS: Kmono correlates to MVO2 in short-term hibernating myocardium when the decreases in aspartate and glutamate or in peak count rate are considered.

Acetates↗