Past, Present, and Future of Dynamic Kidney and Liver Preservation and Resuscitation.

The increased demand for organs has led to the increased usage of "higher risk" kidney and liver grafts. These grafts from donation after circulatory death or expanded criteria donors are more susceptible to preservation injury and have a higher risk of unfavorable outcomes. Dynamic, instead of static, preservation could allow for organ optimization, offering a platform for viability assessment, active organ repair and resuscitation. Ex situ machine perfusion and in situ regional perfusion in the donor are emerging as potential tools to preserve and resuscitate vulnerable grafts. Preclinical findings have ignited clinical organ preservation research that investigates dynamic preservation, its various modes (continuous, preimplantation) and temperatures (hypo-, sub, or normothermic). This review outlines the current status of dynamic preservation of kidney and liver grafts and describes ongoing research and emerging clinical trials.

A new case of familial partial generalized resistance to thyroid hormones: study of 3,5,3'-triiodothyronine (T3) binding to lymphocyte and skin fibroblast nuclei and in vivo conversion of thyroxine to T3.

A clinically euthyroid 30-yr-old man with high serum levels of both total (T4, 14.5 micrograms/dl; T3, 272 ng/dl) and free (FT4, 33 pg/ml; FT3, 9.7 pg/ml) thyroid hormones and inappropriately normal TSH levels, both basally and after TRH stimulation, is described. Peripheral indices of thyroid hormone action and the patient's clinical status were not modified by the prolonged administration of supraphysiological doses of both T4 (up to 900 micrograms/day) and T3 (up to 80 micrograms/day), which decreased but did not completely abolish the TSH response to TRH. However, the TSH response to TRH was normally blunted by dexamethasone administration, which also reduced serum T4 and T3 levels to normal. T3 binding to nuclei of mononuclear leukocytes and cultured skin fibroblasts was normal. The overall pattern demonstrates that the patient was affected by partial peripheral resistance to thyroid hormone action. Study of the patient's family revealed the same hormone pattern in the patient's father, suggesting an autosomal dominant mode of inheritance. An in vivo study performed after the iv injection of tracer doses of [125I]T4 and [131I]T3, demonstrated increased production rates (PR) of both T4 [PR, 113.0 micrograms/day X m2; normal subjects, 55.4 +/- 12.3 (mean +/- SD); n = 13] and T3 (PR, 41.1 micrograms/day X m2; normal subjects, 16.3 +/- 2.7). In vivo conversion of T4 to T3 was also evaluated in the patient; a nearly normal T4 to T3 conversion factor was found (0.3108 vs. 0.2576 +/- 0.0422 in normal subjects). In four hyperthyroid patients, the T4 to T3 conversion factors were similar (0.2932 +/- 0.0600), while the PRs of T4 and T3 were increased (PR of T4, 308.6 +/- 85.6; PR of T3, 110.3 +/- 35.0 micrograms/day X m2) compared to those in the normal subjects.

Assessment of sinus node function in asymptomatic subjects with sinus bradycardia and in symptomatic patients with sino-atrial disease.

Sinus node function was evaluated in 18 patients with sinus bradycardia without complaints (Group I), in 16 patients with sinus bradycardia and/or sinoatrial block with complaints (subgroup IIa) and in 14 patients with the bradycardia-tachycardia syndrome (subgroup IIb). Mean values of corrected sinus node recovery time (CSRT), atrial effective refractory period (AERP) and atrial functional refractory period (AFRP) differentiated significatively asymptomatic subjects of group I from the two subgroups of patients with sinoatrial disease, but failed to differentiate each subgroup from the other one. There was no significative difference in mean sinoatrial conduction time (SACT) between group I and each of the two subgroups. Three patients of subgroup IIa and 1 patient of subgroup IIb had a false negative response after both overdrive and premature programmed atrial pacing. Spontaneous cycle length was directly correlated with the sinus node recovery time and the atrial refractoriness in group I, and with the only sinus node recovery time in subgroup IIb. No direct correlations were observed in subgroup IIa. This suggests a less disturbed sinus node automaticity in bradycardia-tachycardia syndrome.

[Evaluation of sinoatrial conduction time by recording the sinus node potential. Comparison with indirect methods of evaluation]. / Evaluation du temps de conduction sino-auriculaire par enregistrement du potentiel du noeud sinusal. Comparaison avec les méthodes indirectes d'évaluation.

A method of recording the sinus node potential (SNP) has recently been introduced in clinical electrophysiology. The sinoatrial conduction time can now be measured directly (SACTD) as the interval between the onset of the SNP and the onset of atrial activation. We measured the SACTD in 16 normal subjects and in 7 patients with sinus node dysfunction. These values were compared with those obtained by the indirect methods of Strauss et al (SACTS) and Narula et al (SACTN). In normal subjects the SACTD ranged from 50 to 130 ms (average 84,4 +/- 22,35); the SACTS, from 55 to 160 ms (92,9 +/- 29,3), and the SACTN from 70 to 175 ms (113,2 +/- 28,8). In patients with sinus node dysfunction the SACTD ranged from 200 to 290 ms (227 +/- 32,5), the SACTS, from 52 to 198 ms (111,8 +/- 59,3) and the SACTN from 89 to 251 ms (142,3 +/- 63). No significant difference was observed between normal and pathological subjects using the indirect methods of evaluation. However, the SACTD method showed a very significant difference between the two groups (p less than 0,0005) with no overlap. No correlations were observed between the values obtained by the indirect and direct methods of measuring SACT.

[Comparison of Narula's technic of direct and estimated sinoatrial conduction at increasing rates in normal subjects]. / Comparaison chez le sujet normal du temps de conduction sino-auriculaire mesuré directement et estimé par la technique de Narula à fréquences croissantes.

Twenty eight normal subjects in sinus rhythm underwent direct measurement of sinoatrial conduction time (SACTD) by sinus node potential recordings (SNP) and indirect evaluation by Strauss (SACTS) and Narula's methods (SACTN) using the extrastimulus technique. Stimulation in Narula's method was undertaken at three different rates, 3, 6 and 9 beats per minute faster than the spontaneous rate of the subject (SACTN3, SACTN6, SACTN9). The mean values (+/- SD) were as follows: SACTD 84 +/- 18, SACTN3 85 +/- 29, SACTN6 96 +/- 33, SACTN9 101 +/- 36. The mean value of the SACTD was significantly lower than that of the SACTN9 (p less than 0,01) but there were no significant differences between SACTD and SACTN3 and SACTN6. The three values of the SACTN were closely related to each other but not to the values of the SACTD.

Concealed AV junctional extrasystoles simulating second-degree sinoatrial block.

Concealed AV junctional extrasystoles are described which, conducted in a restrograde manner to the sinoatrial junction, interfere with sinus impulses, thus simulating a second-degree, 2:1, sinoatrial block.

Bioavailability of digoxin in capsules.

The authors have studied the bioavailability of a commercially available digoxin solution in capsule. Data obtained were different from that reported by other authors using experimental preparations. Single-dose and steady-state studies evidenced a similar bioavailability for capsules and standard tablets. These results introduce the new problem of the inadequate bioavailability of capsules.

Idioventricular parasystolic rhythms.

A description is given of the electrocardiograms of three subjects with artificial demand pacemakers in whom no inhibition of the idioventricular rhythms occurs, thus causing unusual relationships between the artificial and the spontaneous rhythms. The latter are protected and therefore appear to be parasystolic. In the first two cases, interpolated artificial beats are inscribed in the spontaneous rhythm. In the third case, the spontaneous parasystole is intermittent and alternates with concealed extrasystolic beats originating in the same focus.

[Ventricular tachycardia induced by atrial pacing. Report of one case (author's transl)]. / Tachicardia ventricolare in corso di stimojlazione atriale. Descrizione di un case.

A case of ventricular tachycardia induced by atrial pacing is described. The hypthesis is considered that the arrhythmia could be triggered by direct activation of the ventricles along the preferential conduction pathways of the atria.

Cardiac effects of clomipramine treatment. ECG and left ventricular systolic time intervals.

ECGs and left ventricular systolic time intervals were studied in 26 patients suffering from major depressive disorder treated with clomipramine. ECGs did not show, with one exception, drug-induced changes. The ratio of pre-ejection period to left ventricular ejection time, both corrected for heart rate (PEPc/LVETc), presented no significant changes, as compared with initial findings, in the group of patients considered as a whole. 27% of patients, however, showed individual percent changes greater than 8%, both increases and decreases having been observed. Cardiac findings were in no way related to clomipramine plasma levels.

An unusual PR interval alternans during 2:1 atrio-ventricular block.

In a case of a 2:1 second degree A-V block during sinus rhythm, PR intervals of two different durations occur, either separately or alternating beat-by-beat. The longer intervals are not caused by concealed conduction in the A-V junction of the preceding blocked impulses and the shorter ones are not due to supernormal conduction induced by the blocked impulses. This primary PR interval alternans is alternating from a pathophysiological point of view; it only concerns every other impulse alternately traveling along the faster and slower A-V junctional pathway.

The cardiac electrophysiological effects of nifedipine.

A study was carried out on the electrophysiological effects of a sublingually administered antianginal drug: nifedipine (20 mg). The results show a significant shortening of sinus cycle length from 925 +/- 249 msec to 810 +/- 245 msec, (p less than 0.005) and the disappearance of some interpolation and echo zones. There are no significant effects on the other evaluated parameters of sino-atrial and AV-node function. In one case, during atrial pacing, a second-degree, Wenckebach type, A-V block was present only before nifedipine. The following conclusions were reached: 1. nifedipine has no significant electrophysiological effect on the human heart; 2. the electrophysiological effects observed are probably indirect and related to the vasodilating effect of the drug; 3. the absence of direct cardiac electrophysiological actions may be useful in patients suffering from coronary artery disease and presenting disturbances in the formation and/or conduction of the cardiac impulse.

Electrophysiologic effects of carbochromene in man.

Sinoatrial and atrioventricular node functions were evaluated by the electrode catheter method in 13 patients with coronary artery disease before and 10 min after the i.v. infusion of 80 mg carbochromene. The drug had no effects on sinus node automatism, lengthened the atrial functional refractory period, and restored a 1 : 1 AV conduction at the same atrial rates at which a Wenckebach phenomenon occurred. These effects on atrial functional refractory period and AV conduction may be useful in the treatment of patients with coronary artery disease who present atrial or junctional arrhythmias.