Embryotoxicity Study of Monomeric 4,4'-Methylenediphenyl Diisocyanate (MDI) Aerosol after Inhalation Exposure in Wistar Rats

One of the uses of MDI is as an alternative to formaldehydein the manufacture of furniture, its main route of exposureto humans being by inhalation. There have been no previous studieson the potential prenatal toxic effects of this compound. Toclose this gap in information, gravid Wistar rats, Crl:(WI)BR,were exposed by whole-body inhalation to clean air (control)and to 1, 3, and 9 mg/m3 MDI, respectively, for 6 hr per dayfrom Days 6 to 15 post conception (p.c). Rats were killed onDay 20 p.c. and the following results were obtained: Treatmentcaused a dose-dependent decrease in food consumption in allsubstance-treated groups during exposure, returning to normalvalues after cessation of treatment. The lung weights in thehigh-dose group were significantly increased compared to thesham-treated control animals. Treatment did not influence anyother maternal and/or fetal parameters investigated (maternalweight gain, number of corpora lutea, implantation sites, pre–and postimplantation loss, fetal and placental weights, grossand visceral anomalies, degree of ossification), although aslight but significant increase in litters with fetuses displayingasymmetric sternebra(e) was observed after treatment with thehighest dose of 9 mg/m³. Although the relevance of an increaseof this minor anomaly in doses which cause toxic effects indams (reduced food consumption, increased lung weights) is limitedand the number observed is within the limits of biological variability,a substance-induced effect in the high-dose group cannot beexcluded with certainty. Consequently, a no embryotoxic effectlevel of 3 mg/m³ was determined.     

IS INTRAOPERATIVE ELECTROSTIMULATION OF ERECTILE NERVES POSSIBLE?

PURPOSE: We improved intraoperative conditions to achieve better corpora cavernosal response to stimulation of the erectile nerves. MATERIALS AND METHODS: A total of 18 men undergoing nerve sparing retropubic prostatectomy were evaluated with intraoperative stimulation for identification of the erectile nerves. Intracavernosal pressure was measured directly or via electromyography of the corpora cavernosa. Different kinds of anesthesia were used with or without urapidil. RESULTS: Intracavernosal pressure was recorded in all patients. Use of isoflurane based anesthesia blocked change, and total intravenous anesthesia with propofol resulted in a measurable change in intracavernosal pressure during electrostimulation. However, local urapidil, a potent alpha-blocking agent, doubled or tripled intracavernosal pressure. Electromyography of the corpora cavernosa demonstrated no measurable change. CONCLUSIONS: Intraoperative electrostimulation of erectile nerves requires special anesthesia as well as local blocking of alpha-receptors. The functional anatomy of the erectile nerves is variable.     

Expression of Opioid Receptor Subtypes and Their Ligands in Fibrillating Human Atria

The δ- and κ-receptor subtypes are both abundantly expressed in the human heart and participate in age- and stress-related alterations of cardiac function. Opioid receptor agonists mediate cardioprotection in response to ischemic preconditioning via increased intracellular Ca²⁺ levels, opening mitochondrial K_ATP channels, and PKC activation. We studied the expression of opioid receptor subtypes κ and δ, and of their ligand precursors, proopiomelanocortin (POMC) and preproenkephalin A (PENKA), in human atrial tissue of patients in sinus rhythm (SR), or persistent atrial fibrillation (AF). The mitochondrial size was also compared between the two groups. The atrial mRNA expression of opioid peptide precursors and receptors was assessed by competitive and real-time RT-PCR in 16 patients in AF and 16 patients in SR. Mitochondria were analyzed in the atrial tissue by electron microscopy in four patients in AF and four patients in SR. Both PENKA (SR: 100 ± 33% vs AF: 33 ± 21%; P < 0.05) and κ-receptor mRNA amounts (AF: 78 ± 20% vs SR: 100 ± 11%; P < 0.05) were both decreased in AF in comparison to SR. In addition, POMC mRNA levels were decreased in AF (SR: 100 ± 54% vs AF: 37 ± 26%; P < 0.05), whereas the expression of the corresponding δ-opioid receptor was unchanged (AF: 102 ± 34% vs 100 ± 44%). Mitochondrial size was increased during persistent AF. Persistent AF is associated with the down-regulation of the opioid receptor/ligand expression. This suggests a loss of protective capacity in the fibrillating atrial tissue, resulting in an ultrastructural remodeling of atrial myocytes.     

Electrophysiological Characteristics of Bipolar Membrane Carbon Leads With and Without Steroid Elution Compared With a Conventional Carbon and a Steroid-Fluting Platinum Lead

In a controlled study, the following four bipolar leads with passive fixation were implanted in 46 patients with the Siemens-MuItilog-VVI or Sensolog-VVIR-pacemakers: membrane covered activated porous carbon with steroid elution (Siemens 1402 T, 11 patients) and without (Siemens 1403 T, 15 patients); activated carbon (Siemens 1010T, 10 patients); and platinum with steroid elution (Medtronic CapSure 5026, 10 patients). Stimulation threshold (STH) (assessed by a vario-test), impedance (IMP), and the intracardial R wave potential (IRW) (both gauged by a telemetric method) were measured 1, 5, and 10 days as well as 3 and 6 months after implantation during unipolar and bipolar stimulation, chronaxie rheobase product (CBP) and energy consumption (EC) were systematically determined. Differing insignificantly at the first day after implantation, STH is significantly lower for the 1402 T and CapSure 5026 leads at the tenth day. However, the 1402 T lead shows a significant increase of STH in the follow-up, in contrast to the other leads. The lowest chronic STH was found in the CapSure 5026 lead (CRP is significantly lower in all other leads, too). IMP is significantly lower in the CapSure 5026 lead compared to 1010 T lead. EC does not differ significantly during chronic stimulation in spite of the best possible programming of pulse amplitude and duration. No significant changes of IRW were observed. Unipolar versus bipolar stimulation shows significantly lower STH, CRP, and IMP, differences of EC and IRW were insignificant. In conclusion, the addition of steroid in membrane covered carbon leads protracts the increase of STH, but does not prevent it. The CapSure 5026 lead shows advantageous stimulation characteristics, but energy consumption is not significantly reduced because of low impedance and impossibility of programming an appropriate low output in Multilog pacemakers.     

The Left Subclavian Vein as an Alternative Site for Implantation of the Second Defibrillation Lead

The optimal placement for the second defibrillation lead in a twolead system has never been addressed. We retrospectively reviewed the data of 33 patients with an average age of 59.2 years (range 41–78 years), predominantly mala (n = 29), who underwent implantation of a cardioverter defibrillator (ICD) for treatment of ventricular tachycardia (n = 19) or ventricular fibrillation (n = 14). In all patients an attempt was made to implant an endovenous ICD device (leads only, no subcutaneous patch). In group I (n = 18) the defibrillation anode, a separate unipolar lead, was placed in the common position, the superior vena cava. In group II (n =15) the lead was placed in the left subclavian vein. At least two consecutive shocks reverting ventricular fibrillation at energies ±24J were required for implantation of the ICD device. All shocks were monophasic. The success rate of endovenous defibrillation was significantly higher in group II than in group I (67% vs 28%, P < 0.05). Thus, it could be demonstrated that the position of the defibrillation anode can influence the defibrillation efficacy in transvenous ICD systems. Prospective randomized trials are needed to investigate the optimal position for the second defibrillation electrode, which may gain increasing importance as soon as dual chamber ICDs become available.     

Carvedilol Versus Metoprolol in Patients Undergoing Direct Percutaneous Coronary Interventions for Myocardial Infarction: Effects on QT Dynamicity

Beta-adrenergic blockers exert significant antiarrhythmic activity during ischemia and reperfusion. To further explore the beneficial effects conferred by alpha-1-adrenoceptor blockade on ventricular repolarization dynamicity in the acute phase of myocardial infarction (AMI), we compared carvedilol with metoprolol in the setting of primary percutaneous coronary intervention (PCI). In a prospective study, 100 consecutive patients undergoing primary PCI for AMI were randomized to metoprolol 200 mg/day versus carvedilol 25 mg/day. The first oral dose of study drug was administered and a 24-hour ambulatory electrocardiogram recorded upon hospital admission. Slopes of the linear QT/RR regression were determined before and after reperfusion. A total of 38 recordings of patients treated with metoprolol and 34 recordings of patients with carvedilol were eligible for analysis of QT/RR slopes. The two study groups were similar with respect to age, gender, TIMI perfusion grades, ventricular function, duration of ischemia, and site and size of infarction. Mean RR- and QT-intervals were similar to the metoprolol and carvedilol groups, before and after PCI. Likewise, there was no significant difference in QT/RR slopes between the metoprolol and carvedilol groups before PCI. In contrast, after PCI, there was a trend toward lower QT/RR slopes in the metoprolol group (from 0.18 ± 0.07 to 0.17 ± 0.08), and a significant decrease in QT/RR slopes in the carvedilol group (from 0.17 ± 0.07 to 0.14 ± 0.09). In patients undergoing successful direct PCI for AMI, treatment with carvedilol, in contrast to metoprolol, was associated with a significant decrease in QT–RR slopes, suggesting greater cardiac electrical stability.     

Spontaneous chemical degradation of substance P in the solid phase and in solution

The instability of the undecapeptide substance P (SP), a neuropeptide implicated in several physiological processes, was occasionally observed when the peptide was stored in the solid state or in solution. The aim of the present study was to identify the decomposition products of SP stored as lyophilized peptide or in aqueous neutral solution. The main pathway of the decomposition of SP acetate consists of the subsequent release of N-terminal dipeptides via their diketopiperazines. cyclo(Arg-Pro) and cyclo(Lyys-Pro). In contrast to the decomposition of the acetate of SP, the hydrochloride and trifluoroacetate salts were found to be considerably more stable. Under the studied conditions the release of N-terminal dipeptides dominates over other possible routes of spontaneous modifications, such as S-oxidation and deamidation.     

Quantitative Tissue Doppler Echocardiography: Physiological Nonuniformity of Left Ventricular Transmural Myocardial Wall-Motion Velocities and Gradients

Tissue Doppler echocardiography (TDE) is a new method by which transmural myocardial function can be studied noninvasively. In order to investigate physiology and reproducibility, 24 young, healthy volunteers were examined by M-mode TDE. Nonuniformity of transmural tissue layer velocities became apparent: Subendocardial and subepicardial velocities of the anteroseptal myocardial wall (AW) were 3.5 ± 0.7 and 1.3 ± 0.5 cm/sec (P < 0.0001 , t- test), whereas in the posterolateral wall (PW) values of 3.6 ± 0.6 and 1.2 ± 0.4 cm/sec (P < 0.0001 , t- test ), respectively, were revealed. The ratios, termed "myocardial velocity gradients" as a new indicator of left ventricular performance, were 3.1 ± 1.0 and 3.4 ± 1.1, respectively. AW and PW did not differ (N.S.). Tolerance borders did not overlap, and intraobserver variability did not reach intersubject variability (P < 0.0001, F-ratio test). TDE provides new and more sophisticated insights into left ventricular performance. It seems to be accurate and reliable and therefore worth introducing into the clinical arena.