First-in-man evidence of the mechanistic effects of biventricular pacing on coronary physiology

BackgroundNormal coronary blood flow is principally determined by a diastolic backward travelling decompression (suction) wave. Dyssynchronous heart failure may attenuate suction. We hypothesised that biventricular pacing, by restoring left ventricular (LV) synchronisation and improving LV relaxation, might increase this suction wave and coronary flow.MethodsTen patients with congestive heart failure (nine men; mean age 65 years [SD 12]; mean ejection fraction 26% [SD 7] with left bundle branch block (LBBB, mean QRS duration 174 ms [SD 18]) underwent atriobiventricular pacing at 100 beats per min. LV pressure was measured and wave intensity calculated from invasive coronary flow velocity and pressure, with native conduction (LBBB) and during biventricular pacing at atrioventricular (AV) delays of 40 ms (BiV-40), 120 ms (BiV-120), and separately pre-identified haemodynamically optimal AV delay (BiV-Opt). Data are given as median (IQR).FindingsCompared with LBBB, BiV-Opt enhanced coronary flow velocity time integral (VTI) by 15% (7–25, p=0·007), LV dP/dt_max by 17% (9–22, p=0·005), and _negdP/dt_max by 17% (9–22, p=0·005). The cumulative intensity of the diastolic backward decompression (suction) wave increased by 26% (18–54, p=0·005). Much of the increase in coronary flow VTI occurred in diastole (69% [41–84], p=0·047). The systolic compression waves also increased: forward by 36% (6–49; p=0·022) and backward by 38% (20–55, p=0·022). BiV-120 generated a smaller LV dP/dt_max (by 12% [5–23], p=0·013) and _negdP/dt_max (by 15% [8–40], p=0·009) increase than did BiV-OPT, with LBBB as reference; BiV-Opt and BiV-120 were not significantly different in coronary flow VTI or waves. BiV-40 was no different from LBBB.InterpretationWhen biventricular pacing improves left ventricular contraction and relaxation, it increases coronary blood flow velocity, predominantly by increasing the dominant diastolic backward decompression wave.FundingBritish Heart Foundation.     

Giant Mitochondria with Paracrystalline Inclusions in Paraganglioma of the Urinary Bladder: Correlation with Mitochondrial Abnormalities in Paragangliomas of Other Sites

Mitochondrial abnormalities have received relatively little attention in the ultrastructural evaluation of paragangliomas. Review of the few literature references dealing with this issue, however, reveals that quantitative and qualitative changes of these organelles occur in that context. A bladder paraganglioma is described that was characterized by numerous mitochondria, which in addition displayed giant forms along with matrical paracrystalline inclusions. Upon retrospective review of 12 archival cases of paragangliomas, enlarged and structurally abnormal mitochondria were found in all of them. Although various speculations can be made, the mechanism of formation and the pathophysiologic significance of these abnormal mitochondria remain unknown. From a morphologic diagnostic point of view, however, these abnormalities, which in this case of bladder paraganglioma were also light microscopically evident, can be of significant help in establishing the correct diagnosis.     

The critical role of histology in an era of genomics and proteomics: a commentary and reflection

The role of histologic examination in lymphoma diagnosis has been called into question by proponents of new technologies, such as genomics and proteomics. We review the history and salient features of morphologic evaluation in lymphoid diseases, and discuss the general and specific limitations of mature ancillary techniques, such as immunohistochemistry, flow cytometry, and molecular studies. We then speculate on the future relationship between morphology and the new genomic and proteomic technologies as they become integrated into clinical practice.     

Banff 2011 Meeting Report: New Concepts in Antibody‐Mediated Rejection

The 11th Banff meeting was held in Paris, France, from June 5 to 10, 2011, with a focus on refining diagnostic criteria for antibody‐mediated rejection (ABMR). The major outcome was the acknowledgment of C4d‐negative ABMR in kidney transplants. Diagnostic criteria for ABMR have also been revisited in other types of transplants. It was recognized that ABMR is associated with heterogeneous phenotypes even within the same type of transplant. This highlights the necessity of further refining the respective diagnostic criteria, and is of particular significance for the design of randomized clinical trials. A reliable phenotyping will allow for definition of robust end‐points. To address this unmet need and to allow for an evidence‐based refinement of the Banff classification, Banff Working Groups presented multicenter data regarding the reproducibility of features relevant to the diagnosis of ABMR. However, the consensus was that more data are necessary and further Banff Working Group activities were initiated. A new Banff working group was created to define diagnostic criteria for ABMR in kidneys independent of C4d. Results are expected to be presented at the 12th Banff meeting to be held in 2013 in Brazil. No change to the Banff classification occurred in 2011.     

The Intravascular Survival of Neutrophils Labeled In Vivo

The survival of blood neutrophils labeledin vivo was studied in the calf. Disappearance of labeled neutrophils from the bloodof calves was followed after a period ofcross circulation with their chimeric, immunologically tolerant twins, which hadbeen given tritiated thymidine 6 dayspreviously. Under these conditions, neutrophils were shown to leave the blood ina random exponential fashion, with half-disappearance times of between 6.4 and7.5 hr. Hydrocortisone given to one calf 48hr after cross circulation caused a neutrophilic leukocytosis, during which substantial numbers of labeled neutrophils reappeared in the blood.

Submitted on June 18, 1973 Revised on September 21, 1973 Accepted on September 22, 1973     

Reproducibility of the measurement of the muscle ergoreflex activity in chronic heart failure

BACKGROUND: A causative role for symptom generation in heart failure has been attributed to overactive muscle afferents, metaboreflex and mechanoreflex. We examined the reproducibility of the methods commonly used to assess these reflexes. MATERIAL AND METHODS: Twelve stable heart failure patients (62.8+/-2.4 years) and 18 normals were studied. The metaboreflex was evaluated on both leg and arm exercises, by performing two runs of 5-min submaximal handgrip and leg exercises. On one run the subjects recovered normally (control recovery), while on the other a post-exercise regional circulatory occlusion (PE-RCO) was induced in the exercising limb, to isolate the stimulation of the metaboreceptor after exercise. The metaboreflex was quantified as the difference in ventilation between the PE-RCO and the control recovery periods with respect to rest. The existence of a mechanoreflex was sought by comparing the ventilatory increment per unit of active work (dV(E)/dVO(2) ratio) between leg passive movement and active low level exercise. The coefficients of variation (CV) were computed to express the reproducibility of these reflexes in heart failure. RESULTS: The metaboreflex was overactive in patients vs. normals during both arm (7.2+/-2.8 l/min vs. 0.06+/-0.3 l/min) and leg (5.6+/-1.2 l/min vs. 0.5+/-0.2 l/min) tests. The mechanoreflex was not different between patients and normals: dV(E)/dVO(2) during passive movement 48.9+/-18.3 and 22.4+/-26.5; active exercise 42.3+/-18.4 and 31.9+/-18.7 (P=NS). In patients, the CV for the metaboreflex was 23.4% in the arm and 35.3% in the leg, while for the mechanoreflex test CV was 38.1% during passive movement and 21.1% during active exercise. CONCLUSION: The described method of measuring the muscle reflex activity shows an adequate reproducibility in heart failure patients.