bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of end-systolic pressure-volume relations during acute regional ischemia in situ.
Authors: Kass D A , Marino P , Maughan W L , Sagawa K
Published: June 2011

The influence of extent and location of regional ischemia, baseline left ventricular systolic function, and autonomic reflexes on in situ left ventricular end-systolic pressure-volume relations (ESPVRs) during coronary occlusion were studied in 13 open-chest dogs. Circumflex or left anterior descending arteries were randomly occluded (at proximal or distal sites) for 3 minutes in reflex-blocked (n = 6, hexamethonium/vagotomy) and unblocked (n = 7) animals. Pressure-volume data were obtained by the conductance-catheter technique, with ESPVRs determined by transient inferior vena caval occlusion. Ischemic zone size was estimated for each occlusion by radiolabeled microspheres. The relative influence of each variable on ESPVR change with ischemia was determined by multiple regression analysis. As in previous studies, regional ischemia displaced ESPVRs to the right by an amount that varied directly with ischemic bed size (y = +0.48x, r = 0.76, p less than 0.001). However, in contrast to previous data, coronary occlusion also reduced the ESPVR slope (end-systolic elastance, Ees) in the majority of cases. The extent of slope change was primarily dependent on the baseline elastance (Eesbase), such that the higher the initial elastance, the larger its subsequent reduction for any amount of ischemia (delta Ees = -0.78Eesbase, r = 0.94, p less than 0.001). Active reflexes added an offset constant to this relation (+3.15 mm Hg/ml, p less than 0.001). In addition, Ees fell slightly more with larger ischemic regions. Thus, although previous studies have reported primarily rightward parallel shifts in ESPVR with regional ischemia, the present data also demonstrate that the slope of the relation is often reduced. Greater baseline elastances typical of in situ, as opposed to isolated, ventricles probably explain the differences in apparent responses.
Relation between myocardial glutathione content and extent of ischemia-reperfusion injury.
Authors: Singh A , Lee K J , Lee C Y , Goldfarb R D , Tsan M F
Published: June 2011

The relation between the extent of myocardial injury sustained during reperfusion and total glutathione (GSH) content in the ischemic myocardium was examined in anesthetized open-chest pigs subjected to coronary occlusion for 45 minutes and reperfusion for 2 hours. In pigs infused with saline during reperfusion (n = 6) there was a decrease in myocardial GSH content from 380 +/- 48 micrograms/g in normally perfused myocardium to 182 +/- 36 micrograms/g in the ischemic reperfused myocardium (p less than 0.02). Myocardial infarct size (expressed as a percentage of the ischemic area) was 12.5 +/- 0.8%. There was a delay of recovery of contractile function before returning to 60% of preocclusion value. In pigs pretreated with buthionine sulfoximine (BSO) (n = 5), an inhibitor of cellular GSH synthesis, there was reduction in GSH content to 215 +/- 25 micrograms/gm in normally perfused myocardium and to 77 +/- 8 micrograms/gm in the ischemic reperfused myocardium. The extent of injury was greater as evidenced by an increase in infarct size to 30.4 +/- 4.0% (p less than 0.001), severe destructive changes in subepicardial ultrastructure, which were absent in saline-infused pigs, and persistence of dyskinesia throughout reperfusion. In pigs infused with glutathione intravenously (0.8 gm/kg) at a rate of 6.5 mg/kg/min (n = 6), 5 minutes before and continuously during reperfusion, there was an increase in GSH content to 582 +/- 67 micrograms/g in normally perfused myocardium and to 312 +/- 80 micrograms/g in ischemic reperfused myocardium. The increase in myocardial GSH was associated with a reduction in infarct size to 7.5 +/- 1.3% (p less than 0.05, compared with saline-infused pigs) and an early recovery of contractile function of the ischemic myocardium. GSH infusion into pigs pretreated with BSO (n = 4) failed to increase myocardial GSH content and failed to reduce the extent of myocardial injury. Thus, the extent of myocardial injury sustained during reperfusion is very dependent on the effectiveness of its antioxidant defenses. Markedly increased susceptibility to injury occurs when the GSH content in the ischemic myocardium becomes depleted.
Alleviation of myocardial stunning by leukocyte and platelet depletion.
Authors: Westlin W , Mullane K M
Published: June 2011

Neutrophils accumulate in myocardium rendered ischemic and reperfused. Activated neutrophils release mediators such as metabolites of oxygen that can compromise myocellular integrity and provoke cardiac dysfunction. Although it is established that leukopenia reduces infarct size, the role of leukocytes and the source of free radicals in postischemic contractile dysfunction is unresolved. A carotid left anterior descending coronary-artery extracorporeal circuit without (n = 8) or with a Leukopak filter (n = 6) to deplete the leukocytes and platelets from blood entering the left anterior descending artery was established in the anesthetized, open-chest dog 30 minutes before ischemia. Subendocardial segmental function was monitored by sonomicrometry, and ischemia was produced by stopping flow for 15 minutes followed by 3 hours of reperfusion. Depleting leukocytes by 90 +/- 3.2% and platelets by 100% improved segmental function (from 30.5 +/- 7% to 74.1 +/- 12.7% for control versus leukocyte-depleted dogs, respectively) at 15 minutes of reperfusion. In the leukopenic group, however, there was a progressive decline in contractility to 32.5 +/- 13.8% by 3 hours of reperfusion that was associated with a return of leukocytes and, to a lesser extent, a return of platelets in the extracorporeal blood to 70.2 +/- 21.9% and 15.5 +/- 4.3% of systemic values, respectively. Removal of leukocytes and platelets from blood perfusing the coronary vascular bed only at reperfusion improved contractile function to 67.7 +/- 6.9% at 15 minutes and 54.7 +/- 12.1% at 3 hours (n = 6). Scanning electron microscopy revealed adherent leukocytes in the epicardial coronary arteries of control animals after 3 hours of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Coronary reserve is depressed in postmyocardial infarction reactive cardiac hypertrophy.
Authors: Karam R , Healy B P , Wicker P
Published: June 2011

After a myocardial infarction (MI), the remaining myocardium undergoes a compensatory reactive hypertrophy. Although coronary perfusion to the surviving myocardium can be an important determinant of cardiac function in this setting, there are no available data regarding myocardial blood flow in reactive hypertrophy. Accordingly, we measured coronary blood flow and reserve using radioactive microspheres in rats 4 weeks after induction of an MI by ligation of the left coronary artery. Maximal coronary dilation was induced by Carbochrome, a potent coronary vasodilator, infused at a rate of 0.45 mg/kg/min up to a total dose of 12 mg/kg. Sham-operated rats served as controls. All animals in the infarct group had a large MI affecting 30-51% (average, 41%) of the left ventricle. Left ventricular end-diastolic pressure was significantly elevated (30 +/- 6.5 vs. 8.0 +/- 2.5 mm Hg in sham-operated rats, p less than 0.01) and baseline hemodynamic indexes of cardiac performance were significantly (p less than 0.01) reduced in this group. Myocyte cross-sectional area measurements were used as an index to quantify the degree of reactive hypertrophy and indicated that the infarcted animals had, on average, a 30% hypertrophic response of the surviving left ventricular myocardium. In the infarcted animals, both coronary flow and vasodilator reserve in the surviving myocardium were depressed. Maximal coronary blood flow in the remaining myocardium was significantly lower than that measured in the sham-operated animals (839 and 1,479 ml/min/100 g, respectively; p less than 0.001). Similarly, minimal coronary resistance was significantly higher in the MI group as compared with the sham group (0.12 vs. 0.07 mm Hg/ml/min/100 g, respectively; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Correlation between in vivo transmembrane action potential durations and activation-recovery intervals from electrograms. Effects of interventions that alter repolarization time.
Authors: Haws C W , Lux R L
Published: June 2011

Classic cable theory was used to analyze the relation between the activation-recovery interval measured from unipolar electrograms and transmembrane action potential duration. Theoretic analysis demonstrated that the temporal derivative of the extracellular potential is proportional to a spatial weighting of the third temporal derivative of the transmembrane action potentials along a cable with uniform propagation in a homogeneous medium. Thus, the activation-recovery interval, measured as the interval between times of minimum derivative (Vmin) of the QRS and maximum derivative (Vmax) of the T wave, should be related to action potential duration, measured as the interval between times of Vmax of the upstroke and Vmin of the downstroke of the transmembrane action potential. This relation was examined experimentally in 12 anesthetized dogs. Unipolar electrograms and transmembrane action potentials were recorded simultaneously from sites within 2 mm of each other during control states, cardiac sympathetic nerve stimulation, localized epicardial warming, and graded reductions in myocardial perfusion. The heart was paced from several sites. There was close correlation between activation-recovery interval and action potential duration measurements taken during cardiac sympathetic nerve stimulation and local epicardial warming (r = 0.96 and 0.99 for cardiac sympathetic nerve stimulation and warming, respectively). In five animals in which coronary perfusion pressure was gradually lowered, the variables correlated closely over a range of values from 62 to 212 msec (r = 0.98). However, although the overall correlation was good and mean differences between activation-recovery interval and action potential duration were small, in individual cases there were differences up to 24 msec.(ABSTRACT TRUNCATED AT 250 WORDS)
Relations of the myocardial imaging agents 99mTc-MIBI and 201T1 to myocardial blood flow in a canine model of myocardial ischemic insult.
Authors: Canby R C , Silber S , Pohost G M
Published: June 2011

Myocardial imaging with thallium 201 has proven to be an important clinical procedure to assess the severity of the myocardial ischemic insult. Uptake of 201Tl is related to perfusion to and extraction by intact myocardium. Recently, a newer group of agents based on 99mTc alkyl isonitriles has been developed and appears promising for myocardial imaging. Although the distribution of this new agent has been shown to be related to myocardial perfusion, its dependence on myocardial integrity has not been established. This study compared the distribution of 99mTc-2-methoxy-isobutyl-isonitrile (99mTc-MIBI) with that of 201Tl in a clinically relevant canine model of ischemic insult. Fifteen adult dogs underwent 2 hours of occlusion by left anterior descending coronary artery ligation followed by reperfusion. In one group of dogs, 201Tl and 99mTc-MIBI were administered 5 minutes before 35 minutes of reflow (group 1, n = 5). In the other animals, the agents were given 5 minutes after onset of reflow, and dogs were killed after 10 (group 2, n = 5) and 35 minutes of reperfusion (group 3, n = 5). 99mTc-MIBI activity was significantly correlated with 201Tl activity (r = 0.91, 0.77, and 0.92, for groups 1, 2, and 3, respectively). Both 201Tl and 99mTc-MIBI activities were correlated similarly with blood flow in all models. In groups 1 and 2, 201Tl and 99mTc-MIBI activities correlated directly with microsphere-determined blood flow, whereas in group 3, they correlated inversely. The present study shows that in these models of myocardial ischemic insult, 99mTc-MIBI distribution is closely related to that of 201Tl.
Prostaglandin redirection by thromboxane synthetase inhibition. Attenuation of myocardial stunning in canine heart.
Authors: Farber N E , Gross G J
Published: June 2011

We have previously reported that inhibition of thromboxane synthesis results in an improvement in postischemic function in stunned myocardium of dogs. The purpose of the present study was to investigate further the mechanism by which thromboxane synthesis inhibition improves recovery of function in stunned myocardium (15 minutes of coronary occlusion and 3 hours of reperfusion) in barbital anesthetized dogs. The recovery of regional myocardial wall function (percent segment shortening, % SS) following treatment with two doses (0.5 and 10 mg/kg) of a thromboxane receptor blocker, BM 13.505, given prior to coronary occlusion, was not different from that of a control group (3-hour % SS of pretreatment control, PTC, 12 +/- 11) throughout reperfusion (3-hour % SS of PTC with BM 13.505: 0.5 mg/kg 14 +/- 10; 10 mg/kg, 27 +/- 9). In contrast, the specific thromboxane synthetase inhibitor, dazmegrel (3.0 mg/kg), significantly improved % SS throughout reperfusion (3-hour % SS of PTC, 66 +/- 8). In addition, while dazmegrel produced a marked decrease in thromboxane, 6-keto-PGF1 alpha was significantly increased in coronary venous blood throughout the occlusion and reperfusion period. The cyclooxygenase inhibitor, indomethacin, had no beneficial effect on functional recovery (3-hour % SS of PTC, 5 +/- 6), attenuated the dazmegrel induced shunting to prostacyclin, and completely prevented the beneficial effects of dazmegrel on functional recovery (3-hour % SS of PTC, 17 +/- 12). Thus, a redirection to endogenous cardioprotective prostanoids, such as prostacyclin, appears to be responsible for the beneficial effect of thromboxane synthesis inhibition on postischemic recovery in stunned myocardium whereas thromboxane does not appear to be an important mediator of the stunning phenomenon.
Dual isotope thallium and indium antimyosin SPECT imaging to identify acute infarct patients at further ischemic risk.
Authors: Johnson L L , Seldin D W , Keller A M , Wall R M , Bhatia K , Bingham C O , Tresgallo M E
Published: June 2011

Forty-two patients (28 men and 14 women) with acute myocardial infarction (35 Q, seven non-Q wave) were injected with 2.0 mCi indium 111-labeled antimyosin (AM) monoclonal antibody (111In AM) within 48 hours of the onset of chest pain. Forty-eight hours later (72-96 hours after onset of chest pain), patients were injected with 2.2 mCi thallium 201, and two sets of single-photon emission computed tomography (SPECT) images were obtained simultaneously using dual energy windows set for the 247 keV indium photopeak and the 70 keV thallium peak. Seventeen patients had repeat scans at 4 hours. 111In AM uptake and 201Tl defects were localized to one or more of 24 coronal and sagittal segments. Scans with only 201Tl defects and corresponding 111In AM uptake were classified as matches; scans with unmatched 201Tl defects in addition to matching regions corresponding to electrocardiographic infarct location were classified as mismatches; and scans with 201Tl and 111In AM uptake in the same segments were classified as overlap. Scan patterns were correlated with clinical evidence for residual ischemia occurring within 6 weeks of infarct and including infarct extension, recurrent angina, and positive predischarge low-level or 6-week symptom-limited stress tests and with coronary anatomy. Fourteen patients had only matching patterns (group 1), 23 had mismatches (group 2), and five had 201Tl-111In overlap as the predominant pattern. None of the patients in group 1 had previous myocardial infarction; in each, the matched area corresponded to the Q wave location on electrocardiogram, and none had further in-hospital ischemic events or positive stress tests.(ABSTRACT TRUNCATED AT 250 WORDS)
Improvement in mitral flow dynamics during exercise after percutaneous transvenous mitral commissurotomy. Noninvasive evaluation using continuous wave Doppler technique.
Authors: Tamai J , Nagata S , Akaike M , Ishikura F , Kimura K , Takamiya M , Miyatake K , Nimura Y
Published: June 2011

Evaluation of mitral flow dynamics during exercise is critically important in patients who receive percutaneous transvenous mitral commissurotomy (PTMC) because limited mitral flow during exercise provokes hemodynamic deterioration and involves cardiogenic symptoms in patients with mitral stenosis. To examine mitral flow dynamics during exercise, we applied continuous wave Doppler technique in 20 patients with mitral stenosis. Exercise Doppler study was performed 2 days before and 5 days after PTMC. PTMC increased mitral valve area from 1.0 +/- 0.3 (mean +/- SD) to 1.9 +/- 0.5 cm2 and decreased mean transmitral pressure gradient from 8 +/- 2 to 4 +/- 1 mm Hg at rest. Moreover, PTMC decreased mean transmitral pressure gradient from 21 +/- 6 to 11 +/- 4 mm Hg at submaximal exercise. The extent of an increase in mitral valve area by PTMC correlated with a decrease in the mean transmitral pressure gradient at the submaximal exercise (r = -0.76, p less than 0.01) and that at rest (r = -0.52, p less than 0.05). Heart rate after PTMC during exercise was significantly lower than that before PTMC, indicating that the compensatory mechanism (tachycardia) to increase cardiac output during exercise is less necessary after PTMC. Thus, we conclude that the mitral flow dynamics during exercise is improved, as well as the resting mitral flow dynamics 5 days after PTMC, and that exercise Doppler study enabled us to make a noninvasive evaluation of the mitral flow dynamics in patients who receive PTMC.
Serum aminoterminal type III procollagen peptide reflects repair after acute myocardial infarction.
Authors: Jensen L T , Hørslev-Petersen K , Toft P , Bentsen K D , Grande P , Simonsen E E , Lorenzen I
Published: June 2011

In 16 patients with acute myocardial infarction and in 15 controls, procollagen type III aminoterminal peptide in serum (PIIINP) was measured consecutively. Serum PIIINP was increased on the second to third postinfarction day (p less than 0.01) and remained elevated for more than 4 months. Peak values were observed on the third to seventh postinfarction day. The individual peak changes were correlated to infarction size calculated from serum CK-MB and serum lactate dehydrogenase (p = 0.60, p = 0.02). The changes in distribution of PIIINP-related antigens in serum after gel chromatography were similar to changes observed during wound healing in humans. PIIINP is cleaved off procollagen type III during the biosynthesis of type III collagen, which characterizes the early stages of repair and inflammation. Our findings suggest that serum PIIINP reflects the repair processes and scar formation following acute myocardial infarction. The serum PIIINP alterations in acute myocardial infarction differ essentially from the changes in myocardial enzymes reflecting myocardial injury. Serum PIIINP may therefore provide new and clinically relevant information on the healing of myocardial infarction.
In vivo quantitative ultrasonic evaluation of myocardial fibrosis in humans.
Authors: Picano E , Pelosi G , Marzilli M , Lattanzi F , Benassi A , Landini L , L'Abbate A
Published: June 2011

The aim of this study was to assess in vivo whether the regional ultrasonic reflectivity, evaluated by a real-time integrated backscatter analysis, was related to the local content of connective tissue in human myocardium as estimated by quantitative histology of endomyocardial biopsies. Sixteen patients with presumptive diagnosis of cardiomyopathy were ultrasonically studied by means of an M-mode-based echocardiographic system with quantitative integrated backscatter analysis capabilities. A 2.25-MHz transducer was used. The integrated value of the rectified radiofrequency signal of the interventricular septum was taken as integrated backscatter index and expressed in percent normalized for the pericardial interface (assumed to be 100%). All patients also underwent multiple left ventricular endomyocardial biopsies, which were stained with Masson's trichrome and studied with the use of a computer-assisted image analysis system. The percent integrated backscatter index was significantly higher in the presence of connective tissue area greater than 20% (eight patients) versus less than 20% (eight patients): 51 +/- 25% versus 26 +/- 11%, p less than 0.05. A significant correlation (p less than 0.05, R = 0.55) was found between percent integrated backscatter index and percent connective tissue area. In vivo on-line quantitative ultrasound analysis is feasible in man and reliably identifies variations in the regional extent of fibrosis in human myocardium.
Electrocardiographic changes suggestive of myocardial ischemia elicited by dipyridamole infusion in acute rejection early after heart transplantation.
Authors: Picano E , De Pieri G , Salerno J A , Arbustini E , Distante A , Martinelli L , Pucci A , Montemartini C , Viganò M , Donato L
Published: June 2011

Acute cardiac rejection, syndrome X, and arterial hypertension can induce small vessel damage and, therefore, restriction of coronary reserve in the presence of normal epicardial coronary arteries. A characteristic response pattern to dipyridamole (DIP) infusion has been previously described in syndrome X and arterial hypertension: ST segment depression without any measurable systolic dysfunction. The aim of this study was to establish whether acute cardiac rejection might induce electrocardiographic alterations during DIP infusion. Changes in the 12-lead electrocardiogram and two-dimensional echocardiogram during high-dose DIP infusion (up to 0.84 mg/kg in 10 minutes) were evaluated within 24 hours of endomyocardial biopsy in 14 transplanted patients. A total of 47 biopsy-controlled DIP studies were performed within 5 weeks after cardiac transplantation. For each patient, at least 7 days elapsed between two consecutive studies. Electrocardiographic and echocardiographic tracings were analyzed without prior knowledge of endomyocardial biopsy findings. No remarkable side effects occurred in any case, so that the DIP study could be completed in all patients. A diagnostic (greater than 0.1 mV) ST segment depression was found in 11 studies. The sensitivity and specificity of DIP-induced ST segment depression for the detection of biopsy-proven acute rejection were 72% and 94%, respectively. These data show that DIP stress is feasible and safe in transplanted patients and that acute cardiac rejection can be accompanied by DIP-induced ST segment depression without detectable impairment in systolic function. These changes might provide noninvasive markers for surveillance of rejection.
Relation between localization of coronary artery disease and local abnormalities in ventricular activation during exercise tests.
Authors: Igarashi H , Yamaki M , Kubota I , Ikeda K , Matsui M , Tsuiki K , Yasui S
Published: June 2011

To examine whether or not the location of local abnormalities on body surface isochrone maps reflects the site of myocardial ischemia, 48 coronary artery disease patients without myocardial infarction were studied. Eighty-seven unipolar electrocardiograms distributed over the anterior chest and the back were recorded simultaneously before and after the submaximal treadmill exercise. For each lead, the duration from the QRS onset to the time of the most rapid decrease in QRS voltage was measured (index of ventricular activation [IVA]). Based o the data provided by these 87 leads, IVA isochrone maps (IVA map) in preexercise and in postexercise, as well as IVA maps showing the difference between preexercise and postexercise, were constructed. The IVA was defined as abnormal when it exceeded (mean + 2 SD) the normal range. We called the area with the abnormal IVA, the "+2SD area." In patients having a stenosis in the left anterior descending artery, the +2SD area in each map was located mainly on the left anterior chest, whereas in patients having a stenosis in the right coronary artery, the +2SD area in each map was located mainly on the right lower thoracic surface. Moreover, the +2SD area of patients with both left anterior descending and right coronary artery disease appeared on both the left anterior chest and the right lower thoracic surface. In patients with left circumflex artery disease, however, the location of the +2SD area did not suggest a stenotic site because of its small population. On the other hand, it was difficult to determine the ischemic site from the body surface distribution of ST segment depression.(ABSTRACT TRUNCATED AT 250 WORDS)
Responses of angiographically normal human coronary arteries to intracoronary injection of acetylcholine by age and segment. Possible role of early coronary atherosclerosis.
Authors: Yasue H , Matsuyama K , Matsuyama K , Okumura K , Morikami Y , Ogawa H
Published: June 2011

We examined the response of left coronary arteries to intracoronary injection of acetylcholine (ACh) 50 micrograms in 74 patients by measuring the diameter changes with a videodensitometric analysis system. Patients with angiographically normal coronary arteries were subdivided into a younger group of 26 patients (age, 9-29 years) and an older group of 23 patients (age, 31-68 years). In the younger group, the diameter at the distal segment of the left anterior descending artery (LAD) and at the proximal, middle, and distal segments of the left circumflex artery (LCx) increased significantly (16.7 +/- 19.3%, p less than 0.01, for LAD and 8.0 +/- 18.8%, p less than 0.05; 11.0 +/- 16.1%, p less than 0.01; and 19.8 +/- 17.5%, p less than 0.01, for LCx segments, respectively) in response to ACh. In the older group, on the other hand, the diameter at the proximal and middle segments of LAD and LCx decreased significantly (-20.8 +/- 16.9%, p less than 0.01; and -17.9 +/- 28.4%, p less than 0.01, for LAD segments and -14.6 +/- 17.4%, p less than 0.01; and -11.3 +/- 21.4%, p less than 0.05, for LCx segments, respectively). The dilator response to ACh in the younger group was significantly greater in the distal segment than in the proximal segment in both LAD and LCx (p less than 0.01 for LAD and p less than 0.05 for LCx). The constrictor response to ACh in the older group was significantly greater in the proximal than the distal segment in both LAD and LCx (p less than 0.05 for LAD and LCx, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of nifedipine on left ventricular diastolic function in patients with asymptomatic or minimally symptomatic hypertrophic cardiomyopathy.
Authors: Yamakado T , Okano H , Higashiyama S , Hamada M , Nakano T , Takezawa H
Published: June 2011

We investigated the effects of nifedipine on left ventricular diastolic function in 17 asymptomatic or minimally symptomatic patients with hypertrophic cardiomyopathy by simultaneously measuring left ventricular pressure and volume with a catheter-tipped manometer and biplane cineangiography. Studies were performed before and 20 minutes after sublingual administration of nifedipine (20 mg). Heart rates were held constant (79 +/- 12 beats/min, mean +/- SD) by right atrial pacing. Left ventricular volumes and instantaneous rates of left ventricular volume were derived from frame-by-frame (20-msec) analyses of left ventricular biplane angiograms. Left ventricular peak systolic pressure (from 122 +/- 21 to 108 +/- 13 mm Hg, p less than 0.01 vs. control) and mean aortic pressure (from 96 +/- 15 to 87 +/- 11 mm Hg, p less than 0.01) decreased significantly with nifedipine. With afterload reduction, left ventricular ejection fraction (from 0.69 +/- 0.12 to 0.74 +/- 0.08, p less than 0.01) and cardiac output (from 6.4 +/- 2.0 to 7.2 +/- 2.2 l/mm, p less than 0.05) increased significantly. However, there was a slight but significant increase in left ventricular end-diastolic pressure (from 15 +/- 8 to 18 +/- 8 mm Hg, p less than 0.05). Nifedipine did not improve left ventricular relaxation as assessed by the time constants of isovolumic pressure decay (t1/2, from 39.8 +/- 6.6 to 39.4 +/- 7.7 msec, NS; t1/e, from 53.8 +/- 9.0 to 54.4 +/- 10.7 msec, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamic changes in the peripheral circulation after repeat low density lipoprotein apheresis in familial hypercholesterolemia.
Authors: Rubba P , Iannuzzi A , Postiglione A , Scarpato N , Montefusco S , Gnasso A , Nappi G , Cortese C , Mancini M
Published: June 2011

Repeat low density lipoprotein (LDL) apheresis and blood flow determinations in the forearm and leg were performed in 10 patients (age range, 13-49 years; four male, six female) with familial hypercholesterolemia (eight homozygous, two heterozygous). To perform LDL apheresis, plasma was first separated by a polysulphone hollow fiber filter; then, LDL was selectively removed from plasma by dextran sulphate cellulose beads packed in columns. Blood flows in the forearm and leg were determined at rest and during a reactive hyperemia test (peak flow). This test was performed noninvasively by a strain-gauge plethysmograph with semicontinuous registration of arterial blood flow variables before the first apheresis and 3 weeks after the last of six procedures for apheresis. Resting arterial blood flows in the forearm and leg were slightly increased after repeat LDL apheresis (p less than 0.05). Peak blood flow in the leg significantly increased (+34%, p less than 0.01). No change in peak blood flow in the forearm was observed. Systolic blood pressures were slightly but significantly reduced (p less than 0.05); forearm peripheral resistances were also reduced (p less than 0.05). Flow response was not related to LDL receptor status. Blood and plasma viscosities were determined before and 7 days after the last apheresis. Blood viscosity was significantly reduced after LDL apheresis at shear rates of 11.25-450 sec-1. Plasma viscosity did not change.
Application of a new phased-array ultrasound imaging catheter in the assessment of vascular dimensions. In vivo comparison to cineangiography.
Authors: Nissen S E , Grines C L , Gurley J C , Sublett K , Haynie D , Diaz C , Booth D C , DeMaria A N
Published: June 2011

Tomographic imaging techniques such as ultrasound can provide important information in the evaluation of vascular anatomy. Recent technical advances have permitted fabrication of a small (1.83 mm), phased-array, intravascular ultrasonic imaging catheter capable of continuous real-time, cross-sectional imaging of blood vessels. We used this imaging catheter to compare intraluminal ultrasound with cineangiography in the measurement of vascular dimensions in animals and to assess the intraobserver and interobserver variability of the technique. Segmental deformation of vessel anatomy was produced by stenoses created with a tissue ligature or by balloon dilation. The mean value for measurements of vessel diameter was 5.6 mm by cineangiography and 5.7 mm by intravascular ultrasound. The correlation between cineangiography and ultrasound was close (r = 0.98). Mean cross-sectional area by angiography was 28.8 mm2 and 29.6 mm2 (r = 0.96) by ultrasound. Percent diameter reduction produced by the stenoses averaged 48.4% by cineangiography and 40.1% by ultrasound, and the two methods correlated closely (r = 0.89). Correlation between cineangiography and ultrasound for vessel diameter and area before balloon dilation was closer (r = 0.92 and 0.88) than after balloon dilation (r = 0.86 and 0.81). This difference reflected an increase in measured vessel eccentricity following balloon dilation. These data demonstrate that intravascular ultrasound is an accurate and reproducible method for measurement of vascular diameter and cross-sectional area in vivo. Intravascular ultrasound is capable of accurately identifying and quantifying segmental deformation of vascular dimensions produced by either stenoses or balloon dilation.
Vascular stenting in normal and atherosclerotic rabbits. Studies of the intravascular endoprosthesis of titanium-nickel-alloy.
Authors: Sutton C S , Tominaga R , Harasaki H , Emoto H , Oku T , Kambic H E , Skibinski C , Beck G , Hollman J
Published: June 2011

Percutaneous transluminal balloon angioplasty would be more effective if the rate of recurrent stenosis were reduced. To evaluate the prevention of restenosis after percutaneous transluminal angioplasty, intravascular endoprosthetic stents of titanium-nickel-alloy were implanted transluminally in seven normal and 21 atherosclerotic rabbits. In normal rabbits, a 3.5-mm diameter stent was implanted in the aorta and a 2.5-mm diameter stent in the right iliac artery, which were followed with serial angiograms from 6 weeks (n = 7) to 8 months (n = 4). There was a mean stenosis of 13.1% in the 2.5-mm and 13.6% in the 3.5-mm stent. There was no significant narrowing compared with the adjacent control segments of artery; histopathology showed a thin, fibrous neointima with smooth muscle cells. Each atherosclerotic rabbit was balloon dilated at two separate stenotic sites; each site was 2.0 cm in length. The aortic site (with 28.8 +/- 13.8% mean stenosis [+/- SD]) was dilated with a 3.5-mm balloon, and the iliac site (with 36.5 +/- 14.2% stenosis) was dilated with a 2.5-mm balloon. In each site, an intravascular stent of corresponding diameter and 7-mm length was implanted in one half of the dilated segment, assigned randomly, and the other half served as the angioplasty control. Angiographically observed restenosis rates and the corresponding histopathology were similar in the atherosclerotic segments that had angioplasty alone versus the atherosclerotic segments that had angioplasty plus stenting. The mean neointimal thickness in the aortas and iliac arteries, respectively, measured 247 +/- 181 microns (+/- SD) and 218 +/- 77 microns after 6 weeks (n = 8) versus 321 +/- 168 and 308 +/- 189 microns after 20 weeks (n = 5, p = NS). At 20 weeks follow-up, there was 29.1 +/- 29.8% (median, 16.4%) stenosis in the aortic stent versus 38.9 +/- 24.1% (median, 34.0%) stenosis in the percutaneous transluminal angioplasty control segment of aorta (n = 5, p = NS) and 81.4 +/- 25.5% stenosis in the iliac artery stent versus 89.3 +/- 15.3% stenosis in the PTA control segment of the right iliac artery (n = 5, p = NS). Comparing stenotic arterial segments treated with angioplasty alone with angioplasty plus intravascular stenting in the atherosclerotic rabbits showed that there was no significant difference in either the histopathologic changes or the restenosis rates.
Experimental balloon valvuloplasty of fibrotic and calcific mitral valves.
Authors: Reifart N , Nowak B , Baykut D , Satter P , Bussmann W D , Kaltenbach M
Published: June 2011

This study evaluated the mechanism of valvular area expansion during single- and double-balloon valvuloplasty in fibrotic and calcific mitral valves. Special interest was focused on the morphological features of the valves treated. Mitral valves that appeared unsuitable for commissurotomy were excised in toto at the time of mitral valve replacement in 15 patients. The excised valves were mounted in a fluid-filled chamber with a window for photographic evaluation. The chamber was perfused continuously to ensure maximal valvular opening. The valve was photographed, and the orifice area was measured before and after balloon expansion. In addition, the specimens were examined macroscopically and radiographically with regard to calcium content and degree and localization of fibrosis. These data were correlated with splitting of commissures and with rupture of leaflets. Nine valves were fibrotic, and six were calcific. Dilatation was performed first with a single-balloon catheter (diameter, 2 cm) and then with a double-balloon catheter (diameter, 2 and 1.5 cm). After dilatation with one balloon, the average mitral valve area increased from 0.79 to 1.09 cm2, and with two balloons, average area increased to 1.59 cm2. The single-balloon technique caused commissural splitting in nine valves, stretching in three, partial leaflet rupture in one, and no change in two. After the double-balloon technique, commissural splitting occurred in 12 valves and three leaflets were ruptured where severe fibrosis and calcification were mainly located within the commissures. As a rule, after dilatation with the single-balloon technique, the remaining stenosis was still severe, and after dilatation with the double-balloon technique, the remaining stenosis was moderate.(ABSTRACT TRUNCATED AT 250 WORDS)
Beneficial effects of captopril in acute coxsackievirus B3 murine myocarditis.
Authors: Rezkalla S , Kloner R A , Khatib G , Khatib R
Published: June 2011

To date, there is no universally accepted therapy for viral myocarditis. We investigated the effect of the angiotensin converting enzyme inhibitor captopril on both early and late phases of coxsackievirus murine myocarditis. Mice were infected with coxsackievirus B3 and were divided into two main protocols. Mice in the early treatment protocol (n = 30) were treated on day 1 after infection with either captopril or saline through day 6 of infection and euthanized on day 6 of infection. In the late treatment protocol, mice (n = 60) were treated starting on day 10 of infection through day 30 of infection with either captopril or saline. Mice were killed on days 20 and 30 of infection. In the early treatment protocol, heart weight was 67 +/- 14 mg in the captopril-treated group versus 98 +/- 17 mg in the control group (p less than 0.0001). The degree of inflammation, necrosis, and dystrophic calcification assessed with a semiquantitative histological score was significantly less in the captopril-treated group. The degree of pathological involvement determined by planimetry of histological sections was 8.1 +/- 7.2% for the captopril-treated group versus 22.5 +/- 10.0% for the saline-treated group (p less than 0.0001). In the late treatment protocol, captopril also caused a reduction in heart weight as compared with controls at day 20 (116 +/- 21 mg in captopril-treated group vs. 166 +/- 34 mg in controls, p less than 0.0001) and also at day 30 (136 +/- 23 mg in captopril-treated group vs. 185 +/- 48 mg in controls, p less than 0.004). On days 20 and 30 of infection, the degree of inflammation, necrosis, and dystrophic calcification was similar in both groups. We conclude that captopril is beneficial in acute coxsackievirus B3 murine myocarditis because it reduces heart weight and necrosis when administered early and reduces heart weight when administered in a delayed manner.
Changes of left ventricular diastolic function in exercising dogs without and with ischemia.
Authors: Miyazaki S , Guth B D , Miura T , Indolfi C , Schulz R , Ross J
Published: June 2011

Left ventricular (LV) diastolic function in the absence and presence of regional ischemia was examined in eight conscious dogs chronically instrumented with ultrasonic devices for measuring LV wall thickness and volume. During treadmill exercise, ischemia was induced (hydraulic occluder) to produce less than 10% systolic wall thickening in the ischemic zone. LV filling was assessed by the peak filling rate (PFR), mean filling rates in the first and second halves of filling (mFR1 and mFR2), an early filling index from mitral valve opening to minimal diastolic pressure (PDm), and the percentage of atrial filling. Also, LV relaxation (tau) and wall thinning rates during isovolumetric relaxation and the first and second halves of the filling phase were assessed. During control exercise without ischemia, PDm decreased by 2.61 mm Hg (p less than 0.05) to -1.1 mm Hg and there was a downward shift of the entire LV diastolic pressure-volume (P-V) curve. The LV relaxation rate, PFR, mFR1, and mFR2 were enhanced. Early filling was increased by 116%, the percentage of atrial filling by 118%, and overall diastolic filling by 23% despite a 63% decrease in the filling period. During ischemic exercise, systolic function was depressed compared with the resting state, PDm increased by 4.84 mm Hg (p less than 0.005) associated with a pronounced rightward and upward shift of the early portion of the P-V curve. LV relaxation rate, PFR, and mFR1 were reduced, the early filling index fell sharply by 62% but percentage of atrial filling was unchanged, while overall diastolic filling decreased by 30%. The thinning rate of the control wall was enhanced, whereas that of ischemic wall was depressed. Multiple factors contributed to the markedly impaired early and overall diastolic LV filling during ischemia, including impaired systolic function, reduced relaxation rate, nonuniformity of wall motion, an upward shift of the early diastolic P-V curve, and absence of a compensatory increase in late diastolic filling.
The dependence of the time constant of left ventricular isovolumic relaxation (tau) on pericardial pressure.
Authors: Frais M A , Bergman D W , Kingma I , Smiseth O A , Smith E R , Tyberg J V
Published: June 2011

The purpose of this study was to investigate the dependence of tau, the time constant of left ventricular (LV) isovolumic relaxation, on pericardial pressure and to compare values of tau as determined by the methods of previous investigators and by a standard exponential curve fit. All of the more recent methods involve an additional parameter--the pressure to which the exponential relaxation finally declines (PB, the pressure intercept in the method of Craig and Murgo and the asymptote in the exponential fits). An additional purpose of the study was to determine the relation of these parameters to pericardial pressure. In eight closed-chest anesthetized dogs, tau was calculated from intracavitary (Plv) and transmural LV pressure (Plv = Plv-Pper) by each method as pericardial (Pper) and LV end-diastolic pressure were changed by pericardial infusion and intravenous volume loading. The time constant determined by the method of Weiss et al was dependent on pericardial pressure; the time constants determined by the other methods were not. PB and the asymptotes were found to be similar and to increase almost equally with pericardial pressure. When pericardial pressure was zero, these values were approximately -20 mm Hg. Thus, both these parameters seem to indicate the same baseline pressure, a pressure that increases pari passu with pericardial pressure. Reported changes in the value of tau calculated from intracavitary LV pressure by the method of Weiss et al may reflect factors other than changes in LV diastolic function.
Eosinophils from hypereosinophilic patients damage endocardium of isolated feline heart muscle preparations.
Authors: Shah A M , Brutsaert D L , Meulemans A L , Andries L J , Capron M
Published: June 2011

Persistent eosinophilia in humans is often associated with endocardial damage to the heart, but a causal relation has not been established. We investigated the effect of eosinophils and eosinophil supernatants obtained from eight hypereosinophilic patients on the contractile performance and endocardial morphology of isolated, electrically stimulated cat papillary muscle preparations (n = 16). All these eosinophil suspensions contained high proportions of "hypodense" or "activated" cells. Eosinophils (5-15 x 10(6) ml organ bath) or eosinophil culture supernatants (prepared by overnight incubation at 37 degrees C) when added to papillary muscles produced acute changes in contractile behavior of these muscles identical to the previously reported effects of selective endocardial damage: a reduction in time to peak isometric twitch tension causing a reduction in peak isometric tension but with no significant reduction in rate of tension development or in maximum unloaded shortening velocity. All of these muscle preparations showed severely damaged endocardium at scanning electron microscopy. Addition of eosinophils from hypereosinophilic patients to muscles with selectively damaged endocardium (by previous transient [1-second] exposure to 1% Triton X-100) produced no further change in contractile performance. No significant change in contractile performance or endocardial morphology of papillary muscles (n = 16) was observed after addition of eosinophils (7.5-10 x 10(6] or neutrophils (8-15 x 10(6] from normal subjects or of cell-free culture medium. Thus, activated human eosinophils produce specific morphological and functional changes suggestive of specific damage to endocardium of isolated feline cardiac muscle.
Stretch-induced arrhythmias in the isolated canine ventricle. Evidence for the importance of mechanoelectrical feedback.
Authors: Hansen D E , Craig C S , Hondeghem L M
Published: June 2011

Alterations in loading conditions and muscle length influence the electrophysiology of ventricular myocardium and may play a role in arrhythmogenesis in globally dilated or dyskinetic ventricles. To test the hypothesis that stretch can initiate arrhythmias in normal myocardium, the response to graded mechanical stretch was studied in seven isolated blood-perfused canine ventricles. After eight conditioning contractions produced by His bundle pacing (2 Hz), global stretch of the ventricle was produced by a servocontrolled pump that abruptly increased ventricular volume by a precise amount (delta V) during early diastole and then returned ventricular volume to the initial holding volume (Vi). Ventricular premature contractions were readily produced; ventricular couplets and short runs of ventricular tachycardia were occasionally elicited. The probability of a stretch-induced arrhythmia was determined from multiple alternating sequences in which a stretch of known amplitude (delta V) or no stretch was delivered. As delta V was increased, the probability of a stretch-induced arrhythmia was low initially, increased sharply after a threshold was exceeded, and approaching 100% with physiological volumes. With Vi set to a standard value of 20 ml, corresponding to end-diastolic pressure of 5.3 +/- 5.2 mm Hg (mean +/- SD), the delta V resulting in a 50% chance of a stretch-induced arrhythmia (delta V50) was 15.0 +/- 1.6 ml. A decline in delta V50 was consistently observed when Vi was increased. While delta V50 values were remarkably similar (10.7% coefficient of variation), the pressure at the time the ventricular premature depolarization was triggered was highly variable for different ventricles; this finding suggests that myocardial strain is more important than absolute level of wall stress in the initiation of these arrhythmias. These results demonstrate that myocardial stretch predictably initiates arrhythmias and that the susceptibility to stretch-induced arrhythmias is enhanced by ventricular dilatation. Thus, ventricular ectopy in patients with regionally or globally dilated hearts may arise, in part, by a mechanism of myocardial stretch.
Autoradiographic mapping of calcitonin gene-related peptide receptors in human and guinea pig hearts.
Authors: Coupe M O , Mak J C , Yacoub M , Oldershaw P J , Barnes P J
Published: June 2011

Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide that is a potent coronary vasodilator. Although CGRP is found in high concentrations around coronary arteries, its precise function in the control of coronary vasomotor tone remains unclear. We studied the distribution of specific receptors for CGRP in guinea pig and human hearts and found that the highest concentration of specific receptors for CGRP was in the major coronary arteries, which is consistent with the hypothesis that CGRP is implicated in control of coronary vasomotor tone. Areas of coronary artery with atheroma contained significantly decreased (158 +/- 35 grains/1,000 microns 2 tissue, n = 3) binding sites compared with binding sites in normal arteries (266 +/- 10 grains/1,000 microns 2 tissue, n = 11; p less than 0.001, t test). The decrease in receptors for CGRP around atheroma may predispose these vessels to coronary spasm.