Malte Meesmann

Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR trial).

OBJECTIVESnThe Troponin in Planned PTCA/Stent Implantation With or Without Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Tirofiban (TOPSTAR) trial investigated: 1) the amount of troponin T (TnT) release after nonacute, elective percutaneous coronary intervention (PCI) in patients pretreated with aspirin and clopidogrel; and 2) the effect of additional glycoprotein (GP) IIb/IIIa receptor inhibiton on postinterventional TnT release.nnnBACKGROUNDnNo data are available yet as to whether additional administration of a GP IIb/IIIa receptor antagonist might be beneficial in patients undergoing elective PCI already pretreated with aspirin and clopidogrel.nnnMETHODSnAfter bolus application of the study medication (tirofiban [T] or placebo [P]), PCI was performed followed by an 18-h continuous infusion of T/P. Primary end point of the study was incidence and amount of TnT release after elective PCI after 24 h.nnnRESULTSnA total of 12 h after PCI troponin release was detected in 63% of the patients receiving P and in 40% of the patients receiving T (p < 0.05), after 24 h in 69% (P) and 48% (T) (p < 0.05) and after 48 h in 74% (P) versus 58% (T) (p < 0.08) of the patients. No differences were observed regarding major bleeding, intracranial bleeding or nonhemorrhagic strokes. After nine months a reduction of combined death/myocardial infarction/target vessel revascularization could be observed in the tirofiban group ([T] 2.3% vs. [P] 13.04%, p < 0.05).nnnCONCLUSIONSnTroponin T release occurs after successful intervention in 74% of the patients undergoing elective PCI after 48 h even after pretreatment with aspirin and clopidogrel. The GP IIb/IIIa receptor antagonist tirofiban is able to decrease the incidence of troponin release significantly in this patient population.

Altered Dynamics of Action Potential Restitution and Alternans in Humans With Structural Heart Disease

Background—Restitution kinetics and alternans of ventricular action potential duration (APD) have been shown to be important determinants of cardiac electrical stability. In this study, we tested the hypothesis that APD restitution and alternans properties differ between normal and diseased human ventricular myocardium. Methods and Results—Monophasic action potentials were recorded from the right ventricular septum in 24 patients with structural heart disease (SHD) and in 12 patients without SHD. Standard and dynamic restitution relations were constructed by plotting APD as a function of the preceding diastolic interval. The dynamic restitution relation of both groups showed a steeply sloped segment at short diastolic intervals that was associated with the occurrence of APD alternans. Patients with SHD had a wider diastolic interval range over which APD alternans was present (mean±SEM 68±11 versus 12±2 ms) and showed an earlier onset (168±7 versus 225±4 bpm) and an increased magnitude (20±2 versus 11±2 ms) of APD alternans compared with patients without SHD. The occurrence of APD alternans during induced ventricular tachycardia (6 episodes) and during rapid pacing could be derived from the dynamic restitution function. Conclusions—There are marked differences in the dynamics of APD restitution and alternans in the ventricular myocardium of patients with SHD compared with patients without SHD. These differences may contribute importantly to cardiac electrical instability in diseased human hearts and may represent a promising target for antiarrhythmic substrate modification.

Independent autonomic modulation of the human sinus and AV nodes : evidence from beat-to-beat measurements of PR and PP intervals during sleep

Autonomic Modulation of Sinus and AV Nodes. Introduction: Evidence from animal experiments indicates that the autonomic nervous system may influence the sinus (SA) and atrioventricular (AV) nodes differently. We investigated, therefore, whether there are spontaneous functional differences in the innervation of the SA and AV nodes in man.

DEMONSTRATION OF 1/f FLUCTUATIONS AND WHITE NOISE IN THE HUMAN HEART RATE BY THE VARIANCE-TIME-CURVE: IMPLICATIONS FOR SELF-SIMILARITY

Spectral analysis of heart rate variability is usually performed by Fast Fourier Transform. Here we demonstrate the self-affine properties of the human heart rate using a spectral analysis based on counting statistics. Each QRS complex is considered to be a point event and from the number of events N(Δt) in consecutive time windows Δt the variance is calculated. From the finding that the variance of N(Δt) follows a power law proportional to (Δt)1+b in case of 1/fb noise, it is shown that the variance of the heart rate as determined for windows of length Δt, i.e., N(Δt)/Δt, is proportional to (Δt)b−1. From a 12-day Holter recording, the scaling region could be determined to cover 0.16 to 0.000136 Hz. A function X(t) is self-affine if X(t) and X(rt)/rH have the same distribution functions. From the variance-time-curve, it can be shown that the exponent H is dependent on b with b=2H−1. In young healthy men, the parameter b fluctuates between 0.2 and 1.0 during 24 h and thus determines the self-affine scaling factor H=(b−1)/2 for the amplitude of heart rate, if the time axis is scaled by r. Thus, during periods of 1/f noise, the heart rate scales with H=0, and for periods of almost white noise, with H close to .

A new method for analysis of heart rate variability: counting statistics of 1/f fluctuations

Abstract1/f fluctuations in heart rate are usually measured by spectral analysis using Fast Fourier Transform. Here, we introduce a new method based on counting the number of QRS complexes in time intervals Δt of various length. For a 1/fb spectrum the variance of counts in Δt follows a power-law as gDt1+b. This method is applied to analyze long term fluctuations in heart rate variability in 10 healthy men. The results show periods of 1/f fluctuations with interpolated periods of white noise during night hours.

Selective perfusion of ischemic myocardium during coronary venous retroinjection: A study of the causative role of venoarterial and venoventricular pressure gradients

Coronary venous retroinjection is often associated with preferential distribution of flow to ischemic myocardium. The purpose of this study was to define the mechanism of such retrodistribution of flow. In 24 anesthetized open chest dogs, Monastral blue dye (10 ml) was injected by way of a balloon catheter in the distal great cardiac vein as a marker for retrograde flow distribution. The injection rate (0.6 to 2.4 ml/s) was adjusted such that systolic pressure in the anterior interventricular vein ranged between 60 and 85 mm Hg. In 11 dogs with no ischemia and normal myocardial perfusion pressure (96 +/- 8 mm Hg), no myocardial staining occurred despite retrograde filling of epicardial veins. One minute after occlusion of the left anterior descending coronary artery, dye injections caused selective staining of the cyanotic area in 15 of 18 episodes, sparing the normal myocardium within the zone of retroperfused veins. In five dogs, with the arterial pressure less than 55 mm Hg, retroinjection resulted in homogeneous staining of all the myocardium drained by the retroperfused veins. Selective staining of the ischemic myocardium caused by retroinjection was associated with the following pressure gradients: during systole from the anterior interventricular vein to the occluded coronary artery, 31 to 58 mm Hg, and during diastole from the retroperfused veins to the left ventricular chamber, 9 to 28 mm Hg. There was no diastolic venoarterial gradient in the ischemic myocardium. In normal myocardium, retroinjection did not reverse the arteriovenous pressure gradient. In conclusion, retrograde flow is primarily directed to myocardium with low anterograde perfusion pressure. Selective retrograde penetration of acutely ischemic myocardium can thus be achieved by a mechanism consistent with the development of venoarterial and venoventricular pressure gradients.

Effect of pacing current strength on indexes of myocardial activation in humans: Influence of chronic infarction and polarity of pacing

The effects of current strength (threshold to 20 mA) and pacing polarity (bipolar versus unipolar) on indexes of ventricular activation during endocardial pacing (cycle length 400 to 500 ms) from 10 normal and 17 abnormal left ventricular sites were assessed in 19 patients. Abnormal sites were infarcted and demonstrated an electrogram duration greater than 70 ms and amplitude less than 3 mV during sinus rhythm. Bipolar pacing was performed from poles 1 (cathode) and 3 (1 cm interelectrode distance) of a quadripolar catheter. Unipolar cathodal pacing was performed from the tip electrode (pole 1). Local activation was indexed by the interval from the pacing stimulus to 1) the onset of the QRS complex, 2) the largest rapid deflection of the local electrogram, and 3) the end (total duration) of the local electrogram recorded from poles 2 and 4 of the quadripolar catheter used for left ventricular pacing. Distant activation was indexed by the interval from pacing stimulus to electrograms recorded at the right ventricular apex and outflow tract. Bipolar and unipolar pacing of normal sites produced a modest homogeneous reduction of all activation times by 3 to 11 ms (median) with increments in current strength from threshold (0.8 mA) to 20 mA. Bipolar pacing of abnormal sites showed marked (up to 110 ms) and heterogeneous changes in local (median 22 to 30 ms) as well as distant (median 14 to 23 ms) activation times with increases in current strength from threshold (2.7 mA) to 20 mA.(ABSTRACT TRUNCATED AT 250 WORDS)

On the mechanism of renin release during experimental myocardial ischaemia

Abstract. An increase in plasma renin activity (PRA) following experimental coronary occlusion has previously been demonstrated in anaesthetized and conscious dogs. The purpose of the present study was to analyse the mechanism of this renin release. In two distinct models of myocardial ischaemia in anaesthetized dogs–i.e. occlusion of the left‐anterior descending coronary artery (model A, n= 21) and atrial pacing in the presence of stenosis of the left‐anterior descending coronary artery (model B, n= 23), an increase in arterial PRA was found from 1±68 ± 0±43 to 3±06 ± 0±63 ng ml‐1 h‐1 (model A, ±± SEM, P<0±025) and from 9±87 ± 3±59 to 14±96 ± 4±06 ng ml‐1 h‐1 (model B, P<0±05), respectively. The increase in PRA following coronary occlusion was not blunted by adrenergic beta‐receptor blockade with propranolol (3 mg kg‐1 i.v.; n= 4). Coronary sinus PRA was lower than arterial PRA and the increase in PRA did not occur in nephrectomized dogs (n= 5). The data suggest that myocardial ischaemia induces a release of renin from the kidney which is not mediated by adrenergic beta receptors.

Independent Autonomic Modulation of Sinus Node and Ventricular Myocardium in Healthy Young Men During Sleep

Autonomic Modulation of Sinus Node and Ventricle. Introduction. The aim of this study was to investigate whether autonomic modulation of ventricular repolarization may spontaneousiy differ from that of the sinoatrial node.

Inappropriate Discharge of an Implantable Cardioverter Defibrillator During Atrial Flutter and Intermittent Ventricular Antibradycardia Pacing

Inappropriate Discharge of an ICD. Introduction: Inappropriate discharses of an implantable cardioverter defibrillator (ICD) are troublesome to the patient and sometimes a difficult task for the physician trying; to identify and treat the cause.