Regional myocardial function at the papillary muscle insertion site

The importance of the mitral apparatus to the global left ventricular (LV) function has been suggested in several clinical studies. One recent study reported that chordal transsection induced an unloading of myocardium at the papillary muscle insertion site. We hypothesized that the regional response for afterloading at this site with intact mitral apparatus was different from that at the free wall. We investigated the end-systolic pressure-regional segment length relations (ESPLR) in two anterior LV sites, free wall (FREE) and the papillary muscle insertion site (PAP), during an increasing afterload by aortic occlusion in 7 anesthetized open-chest dogs. To measure the regional segment length at FREE and PAP, two sets of the pair of sonomicrometer crystals were implanted in the same midwall depth at the same circumferential hoop by using an echocardiographic guide. ESPLR both at FREE and PAP were always highly linear in a physiological range (r > or = 0.9). The slope of this relation at FREE (274 +/- 164 mmHg/mm) was significantly steeper than that at PAP (157 +/- 118 mmHg/mm) for each dog (p < 0.05). These data indicate that the regional response for afterloading at PAP loaded by chordal tension is different from that at FREE in the same heart.     

Some ultrastructural features of the myocardial cells in the hypertrophied human papillary muscle

Summary An ultrastructural study using various electron microscopical techniques has been conducted on biopsy material from the hypertrophied papillary muscle of the human heart. About 75% of the myocardial cells were classified as hypertrophic with diameters ranging from 15 m to 53 m. The increased cell diameter appeared to be the result of an elevated amount of mitochondria and contractile material. The hypertrophied myocytes displayed a general ultrastructural organization in many ways similar to that of the normal sized myocytes. However, the former cells were characterized by focal deposits of excess laminar coat material and abnormal Z-band patterns as well as of multiple intercalated discs. The preferential sites for the production of new sarcomere elements appeared to be in the subsarcolemmal and intercalated disc regions. Adjacent myocardial cells were interconnected by collagen bundles, and, by an elaborate collagen-fibril-microthread-granule lattice. The surface folds were linked to each other by surface cables, which probably constituted a separate category of extracellular material of unknown function. Intramembranous particles were abundant in the sarcolemma proper but scarce in the membranes of the sarcoplasmic vesicles. Such particles were also observed in the lipofuscin granular membrane and in the membranes surrounding the lipid droplets. A framework of transverse cytoskeletal filaments interconnected the Z-bands of adjacent myofibrils and anchored the contractile material to the sarcolemma as well as to the nucleus. A large and lobulated nucleus containing well developed nucleoli together with an abundance of sarcoplasmic free and membrane-attached ribosomes, were interpreted as morphological signs of enhanced synthetic activity in the hypertrophied cell. Degenerative phenomena on the other hand were confined to lysosomal degeneration of worn-out cell constituents that were manifested by the numerous lysosomes and aggregates of lipofuscin granules. Abnormal Z-band patterns as seen in the present material were interpreted as an initial stage in the formation of new contractile elements.     

Anti-inflammatory drugs and renal papillary necrosis

The literature on renal papillary necrosis (RPN) associated with the administration of non-steroidal antiinflammatory drugs (NSAID) to rats and man, is reviewed. RPN is almost universally reported after long term administration of NSAID to rats, reports being cited for an indomethacin analog, phenylbutazone, fenamic acids, fenoprofen and sudoxicam. Aspirin will also induce RPN in rats, and is probably the cause of the ‘analgesic nephropathy’ linked to abuse of aspirin/phenacetin combinations in man. RPN is reported at autopsy in human arthritics, but whether this is a facet of the disease, or of long term salicylate ingestion, is not clear. NSAID are rarely implicated in RPN in humans.     

Nephrosis and papillary necrosis after pyelonephritis.

We present a case of nephrotic syndrome complicating acute pyelonephritis in a 45-year-old man. His first attack of acute bacterial pyelonephritis had two unusual features: transient nephrotic syndrome and chronic recurrent episodes of papillary necrosis. The former, which lasted for two weeks, was characterized by edema, excretion of 7.7 g of urinary protein per 24 hours and hypoproteinemia (1.8 g per 100 ml). A percutaneous renal biopsy two weeks after the height of the nephrotic state showed normal glomeruli by light and electron microscopy and immunohistologic studies. Interstitial changes were noted. Over two years the patient has passed approximately 50 fragments, characterized as necrotic tissue containing tubular structures. He has no evidence of diabetes mellitus, urinary-tract obstruction or ureteral reflux, analgesic abuse or atypical vasculitis. He is afebrile but has recurrent bacteriuria despite antibiotics. This case demonstrates that acute pyelonephritis must be added to the list of diseases causing the nephrotic state.     

Experimental pyelonephritis and papillary necrosis in the Gunn rat

Homozygous and heterozygous female Gunn rats show increased susceptibility to experimental urinary infection. The strain develops pyelonephritis after intravesical inoculation of Proteus mirabilis in numbers which fail to induce the lesion in albino rats, and severe pyelonephritis is frequently complicated by papillary necrosis. The basis for this enhanced susceptibility has not been defined, but the occurrence of the phenomenon in both homozygous and heterozygous rats indicates that it is not caused primarily by high plasma levels of unconjugated bilirubin or by the deposition of bilirubin in the tip of the renal papilla. The increased susceptibility of the homozygous Gunn rat to ascending urinary tract infection provides supporting evidence for the suggestion that infection may complicate the natural history of experimental analgesic nephropathy in this strain and is relevant to the clinical association of analgesic nephropathy and urinary infection.     

Spontaneous papillary necrosis in the heterozygous Gunn rat

Spontaneous papillary necrosis develops in aging heterozygous non-jaundiced Gunn rats. The lesion is situated in the subapical or mid papilla and in its earliest stages is manifest by the appearance of amorphous material in the interstitial space. This is seen in plastic-embedded sections taken from rats 6 months old. In its later stages, the accumulation of amorphous material is accompanied by loss of interstitial cells and cyst formation, but there is no associated inflammatory reaction. The largest lesions are found in the oldest rats, but even in these animals the macroscopic appearance of the papilla is normal. Similar papillary changes were not found in albino or homozygous Gunn rats, but in aging albino rats there was loss of papillary interstitial cells without accumulation of amorphous material.     

Isoprenaline-induced myocardial necrosis in dogs

Subcutaneous injections of isoprenaline sulphate in dogs (1-3 mg/kg) resulted in myocardial injury. Good correlation was observed between abnormal ECG recordings, serum enzyme concentrations and myocardial lesions in the acute phase of injury. However, in cases where less extensive myocardial injury was produced due to lower doses of isoprenaline or in cases of the reparative phase of the isoprenaline-induced myocardial injury, serum enzymes were not useful indicators of the change. Similary, ECG recordings taken peripherally also did not show alteration in the reparative phase of the injury in spite of extensive myocardial lesions.     

Enhanced beta-adrenergic response in rat papillary muscle by inhibition of inducible nitric oxide synthase after myocardial infarction

Aim: Myocardial infarction (MI) induces a progressive ventricular remodelling leading to a contractility depression. During the acute phase of MI inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production increases in the heart. The aim of this study was to investigate the role of iNOS in the left ventricular contractility at 3 days after MI. Methods: Wistar rats were divided into: sham operated (SHAM, n = 23), infarction (INF, n = 18); sham operated plus the iNOS inhibitor, S‐methylisothiourea (SMT) 5 mg kg^?1 day^?1, i.p. treatment (SHAM‐SMT, n = 26) and infarction plus SMT (INF‐SMT, n = 22). Concentration–response curves for isoprenaline, Ca²⁺ and frequency–force curve were studied in isolated papillary muscle from left ventricle. Results: After 3 days infarct area was similar between groups. SMT treatment reduced the time to peak tension during frequency–force curve in the infarct group (SHAM = 63 ± 3; SHAM‐SMT = 71 ± 3; INF = 90 ± 4; INF‐SMT = 79 ± 4 ms, P < 0.05) and increased the maximal response to isoprenaline (SHAM = 0.93 ± 0.11; SHAM‐SMT = 1.13 ± 0.1; INF =0.84 ± 0.16; INF‐SMT = 1.49 ± 0.15 g mm^?2, P < 0.05). The response to Ca²⁺ was equally reduced in the INF and INF‐SMT groups. SMT treatment did not change the reduced post‐rest potentiation performed by INF group, but attenuated the plasma nitrite and nitrate (NOx) levels in the INF group without any haemodynamic effect. Conclusion: These finding suggest that at 3 days after MI the iNOS modulates the isolated papillary muscle response to isoprenaline and its inhibition improves the β‐adrenergic inotropic responses.     

Ischemic myocardial cell injury. Prevention by chlorpromazine of an accelerated phospholipid degradation and associated membrane dysfunction.

Ligation of the left coronary artery of an adult rat heart results in the reproducible ischemic cell death of the entire free wall of the left ventricular myocardium. The time course of the development of the cellular changes is biphasic. The subendocardial and subepicardial cells die within the first few hours. The main mass of free-wall myocardium reacts more slowly, with morphologic evidence of irreversible cell injury developing after 12 hours. Measurement of the increases in total free wall Ca++ reflected this biphasic pattern. There was a rapid 3-fold rise in total Ca++ during the first 4 hours. Between 4 and 12 hours the Ca++ was constant. Between 12 and 30 hours there was a second increase that reached a level some 8-10 times the control value. Treatment with chlorpromazine before and subsequent to surgery prevented the appearance of ischemic cell death in the main portion of the free-wall myocardium for at least 24 hours without affecting the reaction of the subepicardial and subendocardial cells. Chlorpromazine also inhibited the second phase of Ca++ accumulation. An accelerated degradation of phospholipids was observed with a 33% decrease in total phospholipids by 12 hours. Phosphatidylethanolamine was reduced by 50% and phosphatidylcholine by 25% without increases in the corresponding lysophospholipids. Chlorpromazine prevented the accelerated degradation and consequent loss of phospholipid. Isolated sarcoplasmic reticulum showed a time-dependent loss of phospholipid with a parallel loss of active Ca++ uptake that reach 60% with a total lipid depletion from these membranes of 33% by 12 hours. Twelve-hour ischemic sarcoplasmic reticulum exhibited a 6--7-fold increase in passive permeability to Ca++. Chlorpromazine protected against the loss of phospholipids, the inhibition of Ca++ uptake, and the increased Ca++ permeability of the sarcoplasmic reticulum. These observations indicate that rat myocardial cells react to lethal doses of ischemia in a manner similar to the reaction of liver cells described previously. In both cases the evidence implies that a disturbance in phospholipid metabolism and its associated membrane dysfunction is the critical alteration that produces irreversible cell injury in ischemia.     

Isoprenaline-induced myocardial necrosis in dogs.

Subcutaneous injections of isoprenaline sulphate in dogs (1-3 mg/kg) resulted in myocardial injury. Good correlation was observed between abnormal ECG recordings, serum enzyme concentrations and myocardial lesions in the acute phase of injury. However, in cases where less extensive myocardial injury was produced due to lower doses of isoprenaline or in cases of the reparative phase of the isoprenaline-induced myocardial injury, serum enzymes were not useful indicators of the change. Similary, ECG recordings taken peripherally also did not show alteration in the reparative phase of the injury in spite of extensive myocardial lesions.