bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nifedipine protects the heart from the acute deleterious effects of cocaine if administered before but not after cocaine.
Authors: Hale S L , Alker K J , Rezkalla S H , Eisenhauer A C , Kloner R A 
Published: June 2012

BACKGROUND
We tested the hypothesis that nifedipine, a calcium channel blocker, could ameliorate the toxic effects of cocaine on the myocardium.

METHODS AND RESULTS
In an initial protocol, anesthetized dogs were pretreated with nifedipine or saline and then administered cocaine (10 mg/kg, i.v. bolus). Coronary blood flow, heart rate, mean arterial pressure, and the first derivation of left ventricular pressure (dP/dt) were measured at baseline, 2 minutes, and 15 minutes after cocaine administration. Nifedipine pretreatment prevented the early cocaine-induced decrease in coronary blood flow and improved left ventricular dP/dt compared with untreated control animals. After cocaine, ejection fraction fell in the saline group to 37 +/- 3% but increased in the nifedipine group to 59 +/- 4% (p less than 0.05). In a second protocol, vehicle or intravenous nifedipine was administered after an infusion of cocaine (10 mg/kg). In contrast to pretreatment, there was no significant improvement in left ventricular function or coronary blood flow in nifedipine-treated versus control animals. Data from the study also suggested that cocaine acts directly on the myocardium. Within seconds of cocaine bolus administration, coronary blood flow in control animals increased to a peak level 59 +/- 14% higher than before cocaine and left ventricular dP/dt decreased by 23 +/- 5%, providing evidence that cocaine causes direct depression of myocardial function independent of a decrease in myocardial blood flow.

CONCLUSIONS
We conclude that nifedipine administered as a pretreatment protects against the depression of myocardial function and decrease in coronary blood flow caused by acute cocaine administration. However, when nifedipine is given after cocaine, no improvement is seen. Cocaine has a direct negative inotropic effect on the heart that is independent of a decrease in coronary blood flow.
A randomized comparison of intravenous heparin with oral aspirin and dipyridamole 24 hours after recombinant tissue-type plasminogen activator for acute myocardial infarction. National Heart Foundation of Australia Coronary Thrombolysis Group.
Authors: Thompson P L , Aylward P E , Federman J , Giles R W , Harris P J , Hodge R L , Nelson G I , Thomson A , Tonkin A M , Walsh W F 
Published: June 2012

BACKGROUND
This study addressed the need for heparin administration to be continued for more than 24 hours after coronary thrombolysis with recombinant tissue-type plasminogen activator (rt-PA).

METHODS AND RESULTS
A total of 241 patients with acute myocardial infarction were treated with 100 mg rt-PA and a bolus of 5,000 units i.v. heparin followed by 1,000 units/hr i.v. heparin for 24 hours. At 24 hours, 202 patients were randomized to continue intravenous heparin therapy (n = 99) in full dosage or to discontinue heparin therapy and begin an oral antiplatelet regimen of aspirin (300 mg/day) and dipyridamole (300 mg/day) (n = 103). On prospective recording, there were no differences in the pattern of chest pain, reinfarction, or bleeding complications. Coronary angiography on cardiac catheterization at 7-10 days showed no differences in patency of the infarct-related artery. The proportion of patients with total occlusion (TIMI grade 0-1) of the infarct-related artery was 18.9% in the heparin group and 19.8% in the aspirin and dipyridamole group. In the patients with an incompletely occluded infarct-related artery, the lumen was reduced by 69 +/- 2% of normal in the heparin group and 67 +/- 2% in the aspirin and dipyridamole group. Left ventricular function assessed on cardiac catheterization and radionuclide study at day 2 and at 1 month showed no differences between the two groups. Left ventricular ejection fraction on radionuclide ventriculography at 1 month was 52.4 +/- 1.2% in the heparin group and 51.9 +/- 1.2% in the aspirin and dipyridamole group.

CONCLUSIONS
We conclude that heparin therapy can be discontinued 24 hours after rt-PA therapy and replaced with an oral antiplatelet regimen without any adverse effects on chest pain, reinfarction, coronary patency, or left ventricular function.
Correlation of circulating von Willebrand factor levels with cardiovascular hemodynamics.
Authors: Penny W F , Weinstein M , Salzman E W , Ware J A 
Published: June 2012

BACKGROUND
Valvular heart disease is associated with a decreased platelet circulating time and a thrombotic tendency. The possibility that these events are related to changes in von Willebrand factor (vWF), a multimeric glycoprotein released from endothelial cells and platelets that mediates platelet adhesion to the vascular subendothelium, has not been examined.

METHODS AND RESULTS
We measured the vWF antigen (vWF:Ag) concentration in 43 patients undergoing cardiac catheterization for the evaluation of mitral (n = 17) or aortic (n = 10) stenosis or nonvalvular heart disease (n = 16). Mean vWF:Ag concentration was significantly higher in patients with mitral stenosis than in those without (212 +/- 84 versus 150 +/- 79 units/dl, p less than 0.02); this elevation was associated with a significant elevation of pulmonary vascular resistance (PVR) in the patients with mitral stenosis (186 +/- 49 versus 133 +/- 81 dynes-sec-cm-5, p less than 0.02). The vWF:Ag levels in the entire group of patients (regardless of the presence or type of valvular disease) varied directly with PVR (r = 0.72, p less than 0.0001) and with pulmonary artery pressure (r = 0.60, p less than 0.0001) and inversely with cardiac output (r = 0.64, p less than 0.0001). Changes in PVR, pulmonary artery pressure, or cardiac output could not be correlated with circulating levels of fibrinogen or beta-thromboglobulin, which may be released from activated platelets, nor with the endothelial cell product tissue plasminogen activator.

CONCLUSIONS
The association of high vWF:Ag levels with increased PVR and decreased cardiac output in patients both with and without mitral stenosis suggests a hemodynamically induced increase in the endothelial release of vWF, which might contribute to a thrombotic tendency in these patients.
Adenosine increases sympathetic nerve traffic in humans.
Authors: Biaggioni I , Killian T J , Mosqueda-Garcia R , Robertson R M , Robertson D 
Published: June 2012

BACKGROUND
Adenosine is an effective hypotensive agent in experimental animals and in anesthetized patients, producing little if any evidence of reflex sympathetic activation. In contrast, adenosine increases systolic blood pressure and heart rate in conscious subjects. To determine whether this response is related to sympathetic activation, we studied the cardiovascular and respiratory effects of adenosine in normal subjects while measuring muscle sympathetic nerve traffic through direct recordings from a peroneal nerve.

METHODS AND RESULTS
Adenosine (80 micrograms/kg/min i.v.) increased heart rate (+32 +/- 3 beats/min), systolic blood pressure (+10 +/- 2 mm Hg), and minute ventilation (+7 +/- 1 l/min). This was accompanied by a dose-dependent increase in muscle sympathetic nerve activity (from 198 +/- 52 to 451 +/- 92 units/min). Adenosine also produced a small, but consistent, decrease in diastolic blood pressure (-6 +/- 3 mm Hg). Adenosine produced a greater increase in sympathetic nerve traffic (145 +/- 32% above baseline) than did nitroprusside (65 +/- 16%) at doses that resulted in equivalent decreased in diastolic blood pressure. Arterial baroreceptor unloading, therefore, could not totally explain the increase in sympathetic traffic produced by adenosine.

CONCLUSIONS
Given the constellation of findings of increased ventilation and sympathetic activity, we, therefore, propose that adenosine increases sympathetic tone by activating afferent nerves, including arterial chemoreceptors. Contrary to the known inhibitory actions of adenosine on central and peripheral efferent systems, this and other reports suggest that adenosine-induced activation of afferent nerves, leading to sympathetic activation, may be a more widespread phenomenon than previously recognized.
Sinoventricular transmission in 10 mM K+ by canine atrioventricular nodal inputs. Superior atrionodal bundle and proximal atrioventricular bundle.
Authors: Racker D K 
Published: June 2012

BACKGROUND
This study was done to determine the electrical properties of the superior atrionodal bundle (SAB) and the proximal atrioventricular bundle (PAVB).

METHODS AND RESULTS
Extracellular potentials associated with electrical activity in the SAB and PAVB were identified in electrograms using adult canine atrial preparations in which the AV node (AVN) and distal AV (His) bundle (DAVB) had been exposed. Intracellular potentials and/or electrograms of the sinoatrial node (SAN), SAB, PAVB, AVN, DAVB, and atrial contractions from a pectinate muscle bundle in the high right atrial wall were recorded. The electrograms contained deflections representing discharge of the specific tissues and atrial potentials from the adjacent or overlying atrial contractile myocardium. In superfusates containing 2.7 mM K+, sequential discharge of the tissues resulted in brief SAN-SAB, PAVB-DAVB, and AVN-DAVB intervals and a major delay after discharge of the SAB. The delay was attributed to activation of the PAVB, as reflected in extracellular PAVB potentials of long duration. Atrial potentials and the onset of the contractile event followed discharge of the SAN and SAB but preceded activation of the PAVB, AVN, and DAVB. After transection of the PAVB-AVN connections, the AVN exhibited automaticity, but the SAB, PAVB, atrial potentials in all of the electrograms, and atrial contractions persisted at the sinus rate. During exposure to 10 mM K+, atrial potentials in all of the electrograms and atrial contractions ceased, indicating electrical quiescence of the contractile myocardium; however, the unique pattern of discharge of the SAB, PAVB, AVN, and DAVB persisted at the SA nodal rate.

CONCLUSIONS
Thus, the SAB and PAVB can be classified as specialized conducting tissues and are intrinsic components of the internodal conductile pathway.
Cardioreparative effects of lisinopril in rats with genetic hypertension and left ventricular hypertrophy.
Authors: Brilla C G , Janicki J S , Weber K T 
Published: June 2012

BACKGROUND
In genetic and acquired hypertension, a structural remodeling of the nonmyocyte compartment of the myocardium, including the accumulation of fibrillar collagen within the interstitium and adventitia of intramyocardial coronary arteries and a medial thickening of these vessels, represents a determinant of pathological hypertrophy that leads to ventricular dysfunction.

METHODS AND RESULTS
To evaluate the benefit of angiotensin converting enzyme inhibition in reversing this interstitial and vascular remodeling in the rat with genetic spontaneous hypertension (SHR) and established left ventricular hypertrophy (LVH), we treated 14-week-old male SHR with oral lisinopril (average dose, 15 mg/kg/day) for 12 weeks. Myocardial stiffness and coronary vascular reserve to adenosine (800 micrograms/min) were examined in the isolated heart; myocardial collagen and intramural coronary artery architecture were analyzed morphometrically. In lisinopril-treated SHR compared with 14-week-old baseline or 26-week-old untreated SHR and age- and sex-matched Wistar-Kyoto (WKY) controls, we found 1) a regression in LVH and normalization of blood pressure, 2) a complete regression of interstitial fibrosis, represented by a decrease of interstitial collagen volume fraction from 7.0 +/- 1.3% to 3.2 +/- 0.3% (p less than 0.025; WKY, 2.8 +/- 0.5%), 3) normalization of myocardial stiffness constant from 19.5 +/- 0.9 to 13.7 +/- 1.3 (p less than 0.025; WKY, 13.8 +/- 2.2), 4) a reversal of intramural coronary artery remodeling, including a decrease in the ratio of perivascular fibrosis to vessel lumen size from 1.4 +/- 0.2 to 0.4 +/- 0.1 (p less than 0.025; WKY, 0.6 +/- 0.1) and medial thickening from 12.3 +/- 0.6 to 7.4 +/- 0.5 microns (p less than 0.005; WKY, 7.4 +/- 0.4 microns), and 4) a restoration of coronary vasodilator response to adenosine from 12.3 +/- 0.9 to 26.0 +/- 1.4 ml/min/g (p less than 0.005; WKY, 21.8 +/- 2.2 ml/min/g). Thus, in SHR with LVH and adverse structural remodeling of the cardiac interstitium, lisinopril reversed fibrous tissue accumulation and medial thickening of intramyocardial coronary arteries and restored myocardial stiffness and coronary vascular reserve to normal.

CONCLUSIONS
These cardioreparative properties of angiotensin converting enzyme inhibition may be valuable in reversing left ventricular dysfunction in hypertensive heart disease.
Selective gene expression in failing human heart. Quantification of steady-state levels of messenger RNA in endomyocardial biopsies using the polymerase chain reaction.
Authors: Feldman A M , Ray P E , Silan C M , Mercer J A , Minobe W , Bristow M R 
Published: June 2012

BACKGROUND
Evaluation of gene expression in failing human heart has been limited by the availability of cardiac tissue.

METHODS AND RESULTS
We used the polymerase chain reaction (PCR) to assess gene expression in small quantities of failing and nonfailing human heart. PCR is a powerful new molecular biological tool that allows a small quantity of DNA to be amplified as much as 1 million-fold. Total RNA was extracted from 3-5 mg samples of human heart and reverse-transcribed to complementary DNA (cDNA). With selected oligonucleotide primers, we used PCR to amplify cDNAs encoding atrial natriuretic peptide, beta-myosin heavy chain, phospholamban, and cytoskeletal beta-actin. To quantify the relative levels of messenger RNA (mRNA) in human heart, a known amount of a control RNA was present in the reverse transcription and PCR reactions. The amount of mRNA in the sample could therefore be assessed in relation to the amount of control product. The control RNA was transcribed from a synthetic DNA template containing primers complementary to those used to amplify the cDNAs of interest. Atrial natriuretic factor mRNA could not be detected in nonfailing human heart but was abundant in ventricular myocardium from failing human heart. In contrast, steady-state levels of phospholamban mRNA decreased, whereas levels of beta-myosin heavy-chain mRNA were unchanged with heart failure.

CONCLUSIONS
Alterations in gene expression in the failing human heart appear to be selective. In addition, the present study suggests that PCR provides a rapid and economical way to quantify the expression of multiple genes of interest in endomyocardial biopsy specimens and may therefore be used to advance our understanding of heart muscle disease.
Thrombolytic therapy with streptokinase stimulates collagen breakdown.
Authors: Peuhkurinen K J , Risteli L , Melkko J T , Linnaluoto M , Jounela A , Risteli J 
Published: June 2012

BACKGROUND
Plasmin is capable of degrading extracellular matrix components such as collagen in vitro. To evaluate the significance of this for in vivo conditions, we set out to study the effect of streptokinase, which acts by converting plasminogen to plasmin, on the serum concentrations of the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal propeptide of type I procollagen (PICP).

METHODS AND RESULTS
Twenty-three patients with suspected acute myocardial infarction were included in the study; 17 of them received thrombolytic therapy, and six were treated conservatively. PIIINP and PICP were assayed with radioimmunoassays. Kinetics of creatine kinase-MB release were determined to differentiate reperfusers from nonreperfusers. Composite curves of creatine kinase-MB release were constructed for different patient subgroups. During streptokinase infusion the serum concentrations of PIIINP increased rapidly, with a maximum mean increase of 50% (from 2.2 +/- 0.2 to 3.3 +/- 0.3 micrograms/l) in 45 minutes. A similar increase was also observed in two patients who received thrombolytic therapy but did not subsequently develop any myocardial infarction determined on the basis of enzyme release. The relative increase in PIIINP during streptokinase treatment was higher in those acute myocardial infarction patients with probable reperfusion than those with nonprobable reperfusion. Corresponding changes in PIIINP were not seen in the control group. Two days later there was a second increase in serum PIIINP for both patient groups. This change coincided with a similar increase in PICP.

CONCLUSIONS
We conclude that streptokinase, probably by activation of plasminogen to plasmin, stimulates the breakdown of type III collagen during thrombolytic therapy. This phenomenon may decrease the risk of rethrombosis of the affected artery if the exposed collagen is responsible for thrombosis formation, but it could also be involved in the development of hemorrhagic complications during thrombolytic therapy. The second increase in PIIINP levels probably indicates type III collagen synthesis of the infarcted area. This investigation represents a pilot study, and more studies on the effects of various thrombolytic agents on interstitial collagen metabolism are obviously needed.
Beta-blocker treatment of dilated cardiomyopathy. Beneficial effect of carteolol in mice.
Authors: Tominaga M , Matsumori A , Okada I , Yamada T , Kawai C 
Published: June 2012

BACKGROUND
The effects of carteolol, a nonselective beta-adrenergic receptor blocker with intrinsic sympathomimetic activity, were compared with those of metoprolol in a murine model of viral myocarditis and dilated cardiomyopathy caused by encephalomyocarditis virus.

METHODS AND RESULTS
In the acute experiment, BALB/c and DBA/2 mice were inoculated with encephalomyocarditis virus. BALB/c mice were then given carteolol at 1 (n = 10), 10 (n = 10), 30 (n = 11), or 100 mg/kg (n = 9) daily, and DBA/2 mice were given carteolol at 1 (n = 9) or 10 mg/kg (n = 9) daily starting the day of inoculation. Controls were given distilled water (n = 23 for BALB/c mice and n = 8 for DBA/2 mice). BALB/c mice were killed on day 7, and DBA/2 mice were killed on day 14. In the subacute experiment, DBA/2 mice were inoculated with the virus and then given carteolol at 1 (n = 12) or 10 mg/kg (n = 16), or distilled water (n = 27) daily, starting on day 14. Mice were killed on day 28. Virus replication, murine survival, heart weight to body weight ratio, and histopathological findings were similar in each group in the acute and subacute experiments. In the chronic experiment, DBA/2 mice were inoculated with the virus and were then given carteolol at 1 (n = 13) or 10 mg/kg (n = 9), metoprolol at 30 mg/kg (n = 9), or distilled water (n = 31) daily, starting on day 14. Mice were killed on day 104. Heart weight to body weight ratio and histopathological scores were significantly lower in mice given carteolol than in the infected control group. Furthermore, left ventricular cavity dimension, left ventricular wall thickness, and myocardial fiber diameter of the left ventricle were significantly reduced in mice given carteolol compared with the control group. Metoprolol did not cause any significant changes compared with the control group.

CONCLUSIONS
This study suggests that carteolol prevents the development of myocardial lesions similar to those in dilated cardiomyopathy after myocarditis in the chronic stage.
Characterization of refractory period extension by transcardiac shock.
Authors: Sweeney R J , Gill R M , Reid P R 
Published: June 2012

BACKGROUND
To better understand the refractory period extension (RPE) produced by transcardiac shocks and its possible role in defibrillation, we measured RPE under various experimental conditions.

METHODS AND RESULTS
Using ventricular pacing in pentobarbital-anesthetized dogs, we characterized RPE in relation to the anatomic site of pacing, the local voltage gradient (LVG) produced by the shocks at the pacing site, and the pacing rate and pacing current used to make the measurements. We also determined if RPE persisted into the next refractory period after the shock and measured RPE at the end of 30-second episodes of acute ischemia to the pacing site, which were caused by occluding the left anterior descending artery. Each anatomic site tested showed RPE, which increased sharply with increasing LVG at lower levels but less sharply at higher LVG. The RPE versus LVG was approximated with an exponential curve that had an exponential constant of about 5-6 V/cm. At faster pacing rates, RPE occurred earlier in the refractory period but was unchanged when expressed as a percent increase of refractory period. RPE did not vary with the pacing current and was present only in the refractory period during which the shock was delivered. The RPE was not significantly altered by acute ischemia. These results show that transcardiac shocks selectively extend the refractory period of tissue proportional to the LVG and the timing of the shock in the refractory period. They are consistent with the concept that RPE prevents depolarization from tissue directly excited by a shock from propagating to tissue that was refractory to that same shock.

CONCLUSIONS
The insensitivity of RPE to short ischemic episodes and the presence of RPE at increased activation rates suggest that RPE might exist under conditions of fibrillation and be a major determinant of the success or failure of defibrillation.
Metabolic basis of primary hypercholesterolemia.
Authors: Vega G L , Denke M A , Grundy S M 
Published: June 2012

BACKGROUND
Hypercholesterolemia is a well-established risk factor for coronary heart disease. However, the mechanisms underlying hypercholesterolemia, elevated low density lipoprotein (LDL) in particular, are not well understood. To determine these mechanisms, we studied LDL kinetics in a group of men with primary hypercholesterolemia.

METHODS AND RESULTS
LDL kinetics in 134 middle-aged men with high-risk levels of LDL cholesterol (more than 160 mg/dl) were compared with kinetics in 16 men with borderline high-risk levels of LDL cholesterol (120-159 mg/dl) and 14 men with heterozygous familial hypercholesterolemia (FH). Patients with primary hypercholesterolemia (non-FH) were further divided into moderate hypercholesterolemia (LDL cholesterol, 160-210 mg/dl; n = 108) and severe hypercholesterolemia groups (LDL cholesterol, more than 210 mg/dl; n = 26). Four factors contributed to increasing LDL cholesterol concentrations above the borderline range to moderately elevated levels: 37 patients had no increase in LDL apolipoprotein (apo) B levels but had abnormally high LDL cholesterol-to-apo B ratios; 14 patients had very low fractional catabolic rates (FCRs) for LDL, similar to FH patients; 35 patients had FCRs for LDL in the borderline range but high production rates for LDL; and 22 patients had a high flux of LDL (high production rates and high FCRs). In general, patients with severe hypercholesterolemia resembled those with moderate LDL elevations, except that their LDL particles were enriched with cholesterol.

CONCLUSIONS
Data from the present study reveal that there are several distinct patterns of LDL metabolism responsible for primary hypercholesterolemia. These patterns can serve as the basis for further investigation to determine the molecular defects responsible for each pattern.