[Cardiac pacemaker therapy for optimizing brain circulation. A possible prevention for cerebrovascular diseases?]. / Herzschrittmacher-Therapie zur Optimierung der Hirndurchblutung. Eine Möglichkeit zur Prävention zerebrovaskulärer Erkrankungen?

HISTORY AND CLINICAL FINDINGS: A 78-year-old patient experienced dizziness, impairment of mnemic and cognitive function, chronic fatigue and recurrent syncope. INVESTIGATIONS: Hypertensive heart disease, reduced left ventricular function, and ventricular ectopia classification Lown IVb was documented. Computed tomography showed minimal brain atrophia. Stenoses of the brain supplying arteries and of other intracranial diseases were excluded. A distinct correlation between cardiac output and cerebral blood flow in correspondence to changes of heart rate were found (cardiac output 4.2 l/min during sinus rhythm, 7.4 l/min during temporary atrial pacing--AAI-Mode with a pacing rate of 90/min; 4.8 l/min--AAI-Mode with a pacing rate of 120/min; cerebral blood flow: 70, 74 and 62 ml/100 g per minute, respectively). Thus, impairment of cerebral blood flow autoregulation can be assumed. TREATMENT AND COURSE: After implantation of a permanent pacemaker the patient was without any complaints. The mnemic and cognitive function improved, dizziness and fatigue disappeared. Synopsis did not occur. 14 months later a sudden onset of complaints occurred caused by atrial fibrillation (heart rate 120/min). Cardiac output and cerebral blood flow were now 4.0 l/min and 35 ml/100 g per minute. After antiarrhythmic drug therapy and restoration of sinus rhythm cardiac output and cerebral blood flow increased and the complaints disappeared again. CONCLUSION: In patients with impaired capacity of cerebral autoregulation a reduced cardiac function and output can induce a reduction of cerebral blood flow. Thus, impairment of mnemic and cognitive function as well as other unspecific neurological deficits can be caused. In these cases pacemaker therapy has to be discussed as an effective therapeutical concept.

Myocardial uptake of technetium-99m-furifosmin (Q12) versus technetium-99m-sestamibi (MIBI).

AIM: This study was performed to compare the myocardial uptake of Tc-99m-furifosmin (Q12) versus Tc-99m-sestamibi (MIBI) in correlation to the whole-body uptake under resting conditions. METHODS: 21 patients with coronary artery disease and no rest ischemia were examined. A whole-body scan was performed 60 min. p.i. under resting conditions. A quantification of the uptake (whole-body, heart and right lung) was done by ROI technique. RESULTS: The heart-to-lung ratio of Q12 (1.56 +/- 0.191) was significantly lower as compared to MIBI (1.94 +/- 0.197; p < 0.01). In contrast, the heart-to-whole-body ratios (Q12 versus MIBI: 0.027 +/- 0.012 versus 0.026 +/- 0.004; p < 0.76) did not differ. The lung-to-whole-body ratio (Q12 versus MIBI: 0.018 +/- 0.009 versus 0.013 +/- 0.002; p < 0.17) were different, but did not reach significance. CONCLUSION: These data show that under resting conditions the total myocardial uptake of Q12 does not differ significantly from that of MIBI. However, the pulmonary uptake of Q12 is slightly higher, resulting in a significant lower heart-to-lung ratio. These findings imply a lower image quality of Q12 compared to MIBI.

Cerebral vasoconstriction during sustained ventricular tachycardia induces an ischemic stress response of brain tissue in rats.

Arterial hypotension can cause cerebral ischemia when the autoregulation of the cerebral circulation is exhausted. We hypothesized that sudden cerebral vasoconstriction induced by moderate hypotensive, but hemodynamically stable, sustained ventricular tachycardias (MHT-VT) further compromises cerebral blood flow (CBF) and induces an ischemic stress response of the brain. CBF-measurements and morphological studies were performed without and with blockade of alpha-adrenergic receptors in order to determine the impact of MHT-VF on brain perfusion and brain tissue. Using a model of MHT-VT, CBF was measured with colored microspheres in 71 rats during control conditions. after the onset of MHT-VT, after the onset of moderate hypotensive hypovolemia (MHH), and after additional non- selective (alpha-blockade with phentolamine and selective alpha1-blockade with prazosin, respectively (0.2-0.4 mg/kg body weight). Plasma catecholamine concentrations were measured in 18 additional rats during control conditions. during MHT-VT and during MHH. The occurrence of heat shock protein (hsp) 72 and activated microglia in the brain was analysed in 18 additional rats in controls, after MHT-VT and MHH. After 20 min of the respective induced hypotension, control conditions were restored for a period of 8 h, by stopping VT or by infusion of isotonic saline solution. CBF was 0.98+/-0.16 (mean+/-S.D.) ml/g/min during control conditions at an arterial pressure of 118+/-13 mmHg, 0.50+/-0.05 ml/g/min (P<0.05 v control) during MHT-VT (76+/-4 mm Hg) and 0.75+/-0.14 ml/g/min (P<0.05 v control and v MHT-VT ) during MHH (71 +/- 8 mm Hg). CBF was better preserved with non-selective alpha-blockade during MHT-VT (0.78+/-0.15 ml/g/min, P<0.05 v MHT-VT and control) as well as with selective alpha1-blockade (0.67+/-0.08 ml/g/min, P<0.05 v MHT-VT and control). Plasma catecholamines were elevated during MHT-VT (P<0.05 v control) but not during MHH (P = N.S. v control). hsp 72 and activated microglia were found in hippocampal regions only after MHT-VT (P<0.05 v control and MHH). These morphological changes were prevented by non-selective alpha-blockade. Stable sustained MHT-VT further reduce the already compromised CBF leading to morphological alterations in the brain which are characteristic of an early ischemic stress response. alpha-Blockade prevents alpha1-adrenergic vasoconstriction and attenuates cerebral hypoperfusion.

[Löffler fibroblastic endocarditis in the thrombotic stages in isolated right ventricular tissue eosinophilia]. / Endokarditis fibroplastica Löffler im thrombotischen Stadium bei isolierter rechtsventrikulärer Gewebe-Eosinophilie.

We report on a male, 31 year old, Turkish patient with an intracardiac mass in the right ventricle, reduction of performance and weight, as well as intermittent fever. No eosinophilia was documented in the peripheral blood; cardiac function was primarily normal. Besides the differential diagnosis of Löffer's endocarditis (endomyocardial fibrosis) an inflammatory disease and a malignant cardiac tumor were suggested. The diagnosis of Löffler's endocarditis could not be confirmed morphologically by echocardiography nor histologically by right ventricular biopsy. Operative removal of the mass lesion was necessary because of fast tumor progression, fulminant pulmonary embolism, and infiltration of the tricuspid valve. Only then, histologically Löffler's eosinophilic endocarditis of thrombotic stage was diagnosed. Antiphlogistic therapy with cortisone was initially performed. With a dose reduction after 6 months, a relapse of the thrombotic mass occurred. Therefore, continuous treatment with cortisone and azathioprine was induced followed by further tumor regression and further clinical stabilization since 8 months of treatment.

Cholinergic and alpha-adrenergic coronary vasomotion [corrected] with increasing ischemia-reperfusion injury.

Ischemia-reperfusion-induced injury of the coronary vasculature could result in an attenuated vasodilator or increased vasoconstrictor tone that might impact on myocardial recovery and viability. In 30 open-chest dogs the left circumflex coronary artery was occluded for 15 or 60 min and then reperfused, and responses to intracoronary acetylcholine, the alpha 1-adrenergic agonist methoxamine, and the alpha 2-adrenergic agonist BHT-933 (n = 10 each) were measured. In the experiments with 60 min of occlusion, triphenyltetrazolium chloride (TTC) staining was used to distinguish reversibly (TTC+) and irreversibly (TTC-) injured myocardium. After 15 min of occlusion, the vasodilator response to acetylcholine was not altered but was significantly reduced in TTC+ subendocardium and midmyocardium after 60 min of occlusion and was further reduced in TTC- subendocardium, midmyocardium, and also in subepicardium. The vasoconstrictor responses to methoxamine and BHT-933 were not altered after 15 or 60 min of occlusion in both TTC+ and TTC- myocardium. Posterior wall thickening was not affected by acetylcholine, methoxamine, or BHT-933. Thus, in reversibly injured myocardium after 15 min of occlusion, cholinergic and alpha-adrenergic coronary vasomotor responses are unchanged. With increasing duration of ischemia, reversibly and even more so irreversibly injured reperfused myocardium are characterized by an impaired cholinergic coronary vasodilation but not an enhanced alpha-adrenergic coronary vaso-constriction.

Attenuation of myocardial stunning by the ACE inhibitor ramiprilat through a signal cascade of bradykinin and prostaglandins but not nitric oxide.

BACKGROUND: Attenuation of myocardial stunning by several angiotensin-converting enzyme (ACE) inhibitors has been demonstrated. However, the signal cascade mediating such protective effect has not been analyzed in detail so far. METHODS AND RESULTS: In a first protocol, we addressed the role of bradykinin and analyzed the effect of the ACE inhibitor ramiprilat without and with added bradykinin B2 receptor antagonist HOE 140 on regional myocardial blood flow (colored microspheres) and function (sonomicrometry). Thirty-two enflurane/N2O-anesthetized open-chest dogs were subjected to 15 minutes of occlusion of the left circumflex coronary artery (LCx) and 4 hours of subsequent reperfusion. Eight dogs served as placebo controls (group 1), and 8 dogs received ramiprilat (20 micrograms/kg IV) before LCx occlusion (group 2). Eight dogs received a continuous intracoronary infusion of HOE 140 [0.5 ng/(mL.min) IC] during ischemia and reperfusion (group 3), and in 8 dogs HOE 140 was infused continuously during ischemia and reperfusion, starting 45 minutes before the administration of ramiprilat (group 4). Mean aortic pressure was kept constant with an intra-aortic balloon, and heart rate did not change throughout the experimental protocols. Under control conditions and during myocardial ischemia, posterior transmural blood flow (BF) and systolic wall thickening (WT) were not different in the four groups of dogs. However, at 4 hours of reperfusion, WT was still depressed in groups 1 (-10 +/- 20% of control [mean +/- SD]), 3 (-18 +/- 12% of control), and 4 (-12 +/- 21% of control), whereas WT in group 2 had recovered to 55 +/- 20% of control (P < .05 versus group 1). BF at 4 hours of reperfusion was not different in the four groups of dogs. Thus, the beneficial effect of ramiprilat on the functional recovery of stunned myocardium was obviously mediated by bradykinin. Since bradykinin stimulates the formation of both prostaglandins and nitric oxide, we tested in a second protocol which of these mediators was further involved in the beneficial effects of ramiprilat. Twenty-four additional dogs were subjected to 15 minutes of LCx occlusion and 4 hours of reperfusion. Six dogs received the cyclooxygenase inhibitor indomethacin (10 mg/kg IV) (group 5) and 6 dogs a combination of indomethacin with ramiprilat (group 6) before LCx occlusion. Six dogs received the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (20 mg/kg IV) (group 7) and 6 dogs a combination of L-NAME with ramiprilat (group 8) before LCx occlusion. BF and WT before and during myocardial ischemia were not different in groups 5 and 6 and groups 7 and 8. However, at 4 hours of reperfusion, WT was still depressed in groups 5 (-10 +/- 38% of control), 6 (-7 +/- 18% of control), and 7 (-12 +/- 14% of control), whereas WT in group 8 had recovered to 47 +/- 28% of control (P < .05 versus group 7). BF at 4 hours of reperfusion was not different in the four groups of dogs. CONCLUSIONS: In summary, the attenuation of stunning by the ACE inhibitor ramiprilat involves a signal cascade of bradykinin and prostaglandins but not nitric oxide.