Acute Cardiovascular Effects of Intravenous Cimetidine

ABSTRACT To assess the acute cardiovascular effects of cimetidine—a widely used histamine-H₍₂₎-receptor antagonist—cuff arterial blood pressure, M-mode echocardiogram of the left ventricle and systolic time intervals were recorded in 10 healthy volunteers before and after 200 mg of cimetidine or isotonic saline given intravenously in a double-blind crossover manner. Neither echocardiograms nor systolic time intervals revealed any significant effects of cimetidine on the left ventricular performance. However, cimetidine decreased slightly the systolic arterial pressure. The maximal effect of cimetidine (7±1 mmHg, mean ± SEM) differed significantly from that of saline (3±1 mmHg, p<0.02). When compared with the pre-injection level, the calculated total peripheral resistance decreased significantly after cimetidine (p<0.01), whereas saline induced no such change. We conclude that a bolus injection of cimetidine does not impair cardiac performance but may induce transient hypotension due to reduction of the total peripheral resistance. This reduction can explain the hypotensive effect of i.v. cimetidine reported in acutely ill patients.     

A New Multisensor Pacing System Using Stroke Volume, Respiratory Rate, Mixed Venous Oxygen Saturation, And Temperature, Right Atrial Pressure, Right Ventricular Pressure, And dP/dt

A new multisensor pacing device using respiratory rate (RR), stroke volume fSV), oxygen saturation (SO2), temperature (T), right atrial pressure (RAPJ, right ventricular pressure (RVPJ and right ventricular dP/dt, has been developed. It consists of a 7F multisensor catheter and an external pacing unit. It allows simultaneous recording of the input signals and the corresponding data can be compared among the different parameters under identical conditions. Furthermore, several parameters can be combined in such a way as to form a new combination better suitable for rate responsive pacing. The response of each parameter to exercise was studied in 12 healthy volunteers (mean age:28 years). Exercise testing was carried out using a bicycle ergometer, with workloads up to 200 W. The dynamic characteristics, response and sensitivity to changes of workloads of each parameter were analyzed and compared to one another. SO₂ proved to be a quick responding parameter (<10 sec) with higher sensitivity in the low exercise range (<75 WJ, T, on the other hand, responded slowly (>30 sec) to exercise changes and had the highest sensitivity in the exercise range beyond 75 W. RR displayed a slow response (>30 sec) and an adequate sensitivity was only found in the upper exercise range (>100 W). SV reacted rapidly to workload changes (<10 sec) but showed poor sensitivity at all exercise levels. RAP, RVP and dP/dt displayed quick responses and constantly good sensitivity throughout the workload range. Furthermore, respiratory rate was easily-derived from the RAP curve. Special algorithms were developed for each parameter so that pacing rate would reproduce sinus rate behavior. We found that SO₂ and all pressure parameter imitated sinus rate response quite well. When using parameter combinations, SO₂ and T proved to be superior. Five patients (mean age 68 years) with third degree AV-block were stimulated temporarily using this system. Compared to fixed rate stimulation [VVI 70], exercise performance improved, using SO₂ as the input parameter for rate response, by 25% to 50%.     

Increased levels of antibodies to food proteins in Down syndrome

An increased level of immunoglobulin A (IgA) antibodies to food antigens has been found in Down syndrome. Biopsy did not show any anomaly of the gut. Increased IgA levels against specific proteins reflect increased transmucosal transport of antigens. The antigens presented may be immunogenic peptides or intact antigens. In this paper, we wished to exclude an institutional cause such as infections and also age differences.     

Synthetic linear and cyclic glucagon antagonists

The synthesis and biological activities of seven new glucagon analogues are reported. The design of com- pounds 2-5 is based on potent antagonists recently reported from this laboratory, where we have focused on modifications in the N-terminal region. In this report we have concentrated specifically on modifications to histidine-1. In addition we have prepared two cyclic compounds 7 and 8 , related to a linear in vivo antagonist [Glu⁹]glucagon, reported by Medeld (Unson et al. (1987) Proc. Natl. Acad. Sci. USA 84 , 4083-4087). The N-terminal modifications involved substitution of His¹ by the unnatural conformationally constrained residue (S)-5,6,7,8-tetrahydro-5-oxoimidazo(1,5-c)pyrimidine-7-carboxylic acid (Toc), desaminohistidine (dHis) and 3-(4-nitrobenzyl)histidine. The structures of the new compounds are as follows. [Toc¹,d -Phe⁴,Tyr⁵,Arg¹²,Lys^17,18,Glu²¹]glucagon ( 2 ); [Toc¹,d Phe⁴,Tyr⁵,Arg¹²,Lys^17,18,Glu²¹]glucagon amide ( 3 ); [3-(4-nitrobenzyl)His¹,d Phe⁴,Tyr⁵,Arg¹²,Lys^17,18,Glu²¹]glucagon ( 4 ); [dHis¹,d -Phe⁴,Tyr⁵,Arg¹²,Lys^17,18,Glu²¹]glucagon ( 5 ); [dHis¹,Glu⁹]glucagon ( 6 ); (desHis¹)glucagon amide ( 7 ); (desHis¹)-glucagon amide ( 8 ). The binding potencies of the linear analogues, as expressed a percentage of glucagon binding, are 2.6 ( 2 ), 0.13 ( 3 ), 0.8 ( 4 ), 0.8 ( 5 ), 2.2 ( 6 ). Both cyclic analogues 7 and 8 show biphasic binding curves. The IC₅₀ values for 7 at the high and low finity sites are 1.5 and 167 nm , respectively (IC₅₀ of glucagon = 1.3 nm ). The IC₅₀ values for ₅₀ at the high and low affinity sites are 4.7 and 3451 nm , respectively. The cyclic analogues are characterized by fast atom bombardment mass spectrometry of endoproteinase ASP-N digests. The specificity of the enzyme used in these studies enables differentiation of isomers of the cyclic glucagon analogues which differ only in the position of cyclic amide bond. Analogues 2,3 and 5–8 are glucagon receptor antagonists with respect to the glucagon receptor coupled to the adenylate cyclase (AC) system. Analogue 4 is a partial agonist (5.7% compared to glucagon) of AC. Introduction of unusual amino acids which do not contain a primary α-amino group such as Toc at the N-terminus is expected to increase in vivo metabolic stability by protecting against degradation by aminopeptidases.     

Clinical Performance of the St. Jude Medical Riata Defibrillation Lead in a Large Patient Population

Clinical Performance of the St. Jude Medical Riata Defibrillation Lead in a Large Patient Population . Objective: The purpose of this large multicenter study was to evaluate the long‐term reliability of an implantable cardioverter defibrillator (ICD) lead to determine the incidence of adverse events (AEs). Background: A recent concern has been the performance of cardiac defibrillator leads. There have been conflicting reports regarding the rate of lead perforation and other AEs. Methods: Medical records from patients implanted from 6‐1‐2001 to 11‐27‐2007 with the St. Jude Medical Riata family of RV leads at 23 US (N = 12,969) and 5 German (N = 2,418) centers were reviewed for chronic lead‐related AEs. These included perforation, dislodgment, conductor fracture and insulation damage. The mean follow‐up period was 18.0 months. AEs were defined as those that required Riata lead revision, extraction, or replacement. Results: The incidence of lead AEs was <1% for each AE type. Perforation occurred in 0.38%, dislodgement in 0.93%, conductor fracture in 0.18%, and insulation damage in 0.21% of patients studied. Conclusions: During the follow‐up of the 15,387 patients with Riata leads, the incidence of AEs which included perforation, dislodgement, conductor fraction and insulation damage was low and within the range of what is considered clinically acceptable. (J Cardiovasc Electrophysiol, Vol. 21, pp. 551‐556, May 2010)