Ventricular and Dual Chamber Pacing for Treatment of Carotid Sinus Syndrome

Thirty-nine consecutive patients with recurrent syncope and either cardioinhibitory or mixed type carotid sinus syndrome were studied to determine the efficacy of ventricular (VVI) pacing in 16, and dual chamber (DDD/DVI) in 23 patients. Only those patients affected by the isolated vasodepressor form were excluded. Follow-up lasted 12 ± 5 months. Symptoms were totally eliminated in 67% of patients and ameliorated with persistence of minor symptoms in 33%. All patients underwent an initial 2-month follow-up in the VVI mode. Evaluation of the 19 patients who remained symptomatic and the 20 who became asymptomatic with VVI pacing demonstrated that factors observed prior to pacemaker implant were related to failure of the VVI mode. These included symptomatic pacemaker effect (42% vs 0%), mixed carotid sinus syndrome (95% vs 65%), orthostatic hypotension (47% vs 15%), or ventriculoatrial conduction (68% vs 38%). In the 23 patients with dual chamber pacing, random 2 month comparisons were performed between VVI and DVI/DDD pacing. The dual chamber mode was preferred by 14 patients, none preferred the VVI mode and nine noted no difference. Comparison of the two groups found that the factors linked to DVI/DDD preference were symptomatic pacemaker effect (50% vs 0%), ventriculoatrial conduction (78% vs 44%), or orthostatic hypotension (50% vs 11 %). VVI pacing is efficacious in a high proportion of patients affected by cardioinhibitory or mixed carotid sinus syndrome. The identification of causes of VVI pacing failure allows determination of those who will benefit from VVI pacing and those who should have DVI/DDD. VVI pacing is suggested for the cardioinhihitory type with no symptomatic pacemaker effect and for the mixed type with no symptomatic pacemaker effect or orthostatic hypotension or ventriculoatrial conduction. Dual chamber pacing should be used in all other instances.     

Solid-phase synthesis of the native sequence of horse heart cytochrome c-(66–104)-nonatriacontapeptide and of a C-terminal carboxyamide analog selectively modified at Met-80

The peptide corresponding to the (66–104) sequence of horse heart cytochrome c and its carboxyamide analog, selectively modified at the critical Met⁸⁰ residue, have been synthesized by stepwise solid-phase methods on PAM and BHA resins respectively. The correctness of the growing peptide chain as well as the homogeneity of the final products have been monitored by several analytical methods including quantitative Edman degradation. After HF cleavage both peptides were purified by semipreparative HPLC. The overall yields were 24% for the native (66–104) and 10% for the carboxyamide analog. The homogeneity of the purified synthetic peptides have been determined by different criteria including HPLC, amino acid composition, Edman degradation, electrophoresis, and tryptic peptide mapping. The synthetic fragments have been utilized for preliminary semisynthesis experiments with the native [Hse〉⁶⁵](1–65)H heme-sequence.     

Synthesis and biological activity of carboxyl terminally extended dermorphins

Dermorphinoyl(DMR)-glycine, DMR-sarcosine and DMR-glycyl-arginine have been prepared in order to examine the effect of C-terminal extension of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH₂) on opioid activity. On GPI preparation the addition of Gly, Sar, or Gly-Arg to the carboxyl terminus of dermorphinoic acid was detrimental to μ activity: dermorphinoyl-derivatives, in fact, retain only 5–20% of dermorphin potency. Following intracerebroventricular administration (tail-flick test), whereas the analgesic activities of compounds showed the trend dermorphin >DMR-Sar> DMR-Gly-Arg>DMR-Gly>morphine, the nonapeptide displayed highest activity after subcutaneous injection in mice: DMR-Gly-Arg was 2.5 and 10 times more potent than dermorphin and morphine, respectively.     

Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation

Endothelial microparticles (EMP) released from activated or apoptotic endothelial cells (EC) are emerging as useful markers for detection of EC dysfunction. Our recent observation that EMP carry von Willebrand factor (vWf) led us to investigate their interaction with platelets. EMP were incubated with normal washed platelets in the presence or absence of ristocetin, then platelet aggregates were measured by flow cytometry. In the absence of ristocetin, negligible EMP conjugated with platelets (< 5%) but in the presence of ristocetin (1 mg mL(-1)), EMP induced up to 95% of platelets to aggregate. EMP-platelet interaction was 80% blocked by anti-CD42b, or by 0.1 microm filtration to remove EMP. Platelet aggregates induced by normal plasma or high molecular weight vWf (Humate-P) dissociated 50% within 15-25 min following 1:20 dilution. In contrast, aggregates formed with EMP persisted two- to threefold longer with the same treatment, indicating greater stability. A similar degree of prolongation of dissociation was observed using plasma from thrombotic thrombocytopenic purpura (TTP) patients compared with normal plasma. Addition of EMP to plasma from severe von Willebrand disease restored his ristocetin-induced platelet aggregation. Multimer analysis of vWf on EMP showed unusually large vWf (ULvWf). In summary, EMP carries ULvWf multimers, promote platelet aggregates, and increase the stability of the aggregates thus formed.     

Long-term Reproducibility of Response to Noninvasive Programmed Cardiac Stimulation in Spontaneous, Sustained Ventricular Tachycardia Treated with Amiodarone Therapy

A total of 73 noninvasive serial electrophysiological studies were carried out in 12 patients with spontaneous sustained ventricular tachycardia, inducible in spite of chronic treatment with amiodarone, in order to verify the effect of this drug on the long-term reproducibility of the test. A ventricular tachycardia was induced in 72 of 73 times; in 59% of cases, the clinical form was induced. In 8 of 12 patients, two or more types or morphologies of ventricular tachycardia could be induced. The induction modes (driving rate and number of extrastimuli) changed considerably in different studies. During a follow-up of 12 ± 6 months, 5 out of 12 patients had spontaneous relapses. We observed no differences between these patients and the others regarding inducibility, types and morphologies of the induced tachycardias, or induction modes. Therefore, when ventricular tachycardia is inducible in spite of chronic amiodarone therapy, it is always inducible during follow-up, even if a great intrapatient change of type and the morphology of induced tachycardias and induction modes is observed. However, since similar electrophysiological features are present in patients with and without spontaneous recurrence of ventricular tachycardia, serial electrophysiological studies are of little value in predicting the clinical outcome.     

Synthesis and properties of chemotactic peptide analogs I. Crystal structure and molecular conformation of HCO-Met-Leu-Ain-OMe

HCO-Met-Leu-Ain-OMe (2), an analog of the chemotactic peptide HCO-Met-Leu-Phe-OH, containing the conformationally blocked residue of the 2-aminoindane-2-carboxylic acid (Ain) has been synthesized and its crystal and molecular conformation has been determined. Crystals of 2 are monoclinic, space group P2₁, with a = 15.059(7), b = 18.548(7), c = 9.600(4)Å;β= 85.04(3). The structure has been solved by direct methods and refined to R = 0.069 for 2813 independent reflections with I > 2.5σ(I). Two independent molecules A and B have been found in the asymmetric unit of the crystal of 2. Their conformation can be described as extended at the Met and Leu residues, but folded at the C-terminal Ain residue. The helical folding is left- and right-handed in the A and B molecule, respectively. The crystal packing is characterized by ribbons of intermolecular hydrogen bonded molecules extended along the c direction. The constrained analog 2 is highly active in the superoxide production, thus indicating that a stabilization of a helical folding at the C-terminal region of chemotactic tripeptides maintains the activity. The orientation of the aromatic ring, with respect to its adjacent backbone atoms, does not seem critical for the activity.